OBJECTIVE: To observe the neuroprotective effect of 6-shogaol (6-SH) in global cerebral ischemia/reperfusion injury (CIRI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in rats. METHODS: Computer-aided molecular docking was used to determine whether 6-SH could spontaneously bind to death-associated protein kinase 1 (DAPK1). SPF-grade male SD rats were randomly divided into a sham group (n = 5), a CPR group (n = 7), and a CPR+6-SH group (n = 7). The CPR group and CPR+6-SH group were further divided into 12-, 24-, and 48-hour subgroups based on observation time points. A rat model of global CIRI after CA-CPR was established by asphyxiation. In the sham group, only tracheal and vascular intubation was performed without asphyxia and CPR induction. The CPR group was intraperitoneally injected with 1 mL of normal saline immediately after successful modeling. The CPR+6-SH group received an intraperitoneal injection of 20 mg/kg 6-SH (1 mL) immediately after successful modeling, followed by administration every 12 hours until the endpoint. Neurological Deficit Score (NDS) was recorded at each time point after modeling. After completion of observation at each time point, rats were anesthetized and sacrificed, and brain tissue specimens were collected. Histopathological changes of neurons were observed under light microscopy after hematoxylin-eosin (HE) staining. Ultrastructural changes of hippocampal neurons and autophagy were observed by transmission electron microscopy (TEM). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression levels of DAPK1, vacuolar protein sorting 34 (VPS34), Beclin1, and microtubule-associated protein 1 light chain 3 (LC3) in brain tissues. Western blotting was used to detect protein expression levels of DAPK1, phosphorylated DAPK1 at serine 308 (p-DAPK1 ser308), VPS34, Beclin1, and LC3. Immunofluorescence was used to observe Beclin1 and LC3 expression in brain tissues under a fluorescence microscope. RESULTS: Molecular docking results indicated that 6-SH could spontaneously bind to DAPK1. Compared with the sham group, the NDS scores of the CPR group rats were significantly increased at all modeling time points; under light microscopy, disordered cell arrangement, widened intercellular spaces, and edema were observed in brain tissues, with pyknotic and necrotic nuclei in some areas; under TEM, mitochondria were markedly swollen with intact membranes, dissolved matrix, reduced or disappeared cristae, vacuolization, and increased autophagosomes. Compared with the CPR group, the NDS scores of the CPR+6-SH group rats were significantly decreased at all modeling time points; under light microscopy, local neuronal edema and widened perinuclear space were observed; under TEM, mitochondria were mostly mildly swollen with intact membranes, fewer autophagosomes, and alleviated injury. RT-qPCR results showed that compared with the sham group, mRNA expression levels of DAPK1, VPS34, Beclin1, and LC3 in brain tissues were significantly upregulated in all CPR subgroups, with the most pronounced changes at 24 hours. Compared with the CPR group, the CPR+6-SH group showed significantly lower mRNA expression of the above indicators at each time point [24 hours post-modeling (relative expression): DAPK1 mRNA: 3.41±0.68 vs. 4.48±0.62; VPS34 mRNA: 3.63±0.49 vs. 4.66±1.18; Beclin1 mRNA: 3.08±0.49 vs. 4.04±0.22; LC3 mRNA: 2.60±0.36 vs. 3.67±0.62; all P < 0.05]. Western blotting results showed that compared with the sham group, the protein expression levels of DAPK1, VPS34, Beclin1, and LC3 in all CPR subgroups were significantly increased, while the expression of p-DAPK1 ser308 was significantly decreased, with the most pronounced changes observed in the CPR 24-hour subgroup. Compared with the CPR group, the CPR+6-SH subgroups exhibited significantly reduced protein expression of DAPK1, VPS34, Beclin1, and LC3 [24-hour post-modeling: DAPK1/β-actin: 1.88±0.22 vs. 2.47±0.22; VPS34/β-actin: 2.55±0.06 vs. 3.46±0.05; Beclin1/β-actin: 2.12±0.03 vs. 2.87±0.03; LC3/β-actin: 2.03±0.24 vs. 3.17±0.23; all P < 0.05]. Conversely, the expression of p-DAPK1 ser308 was significantly upregulated in the CPR+6-SH group compared to the CPR group [24-hour post-modeling: p-DAPK1 ser308/β-actin: 0.40±0.02 vs. 0.20±0.07, P < 0.05]. Under the fluorescence microscope, fluorescence intensities of Beclin1 and LC3 in the CPR 24-hour group were significantly higher than those in the sham 24-hour group; compared with the CPR 24-hour group, the CPR+6-SH 24-hour group showed significantly reduced fluorescence intensities of Beclin1 and LC3. CONCLUSION 6-SH inhibited the expression of DAPK1, alleviated excessive autophagy after global CIRI following CA-CPR in rats, and exerted neuroprotective effects. The mechanism may be related to phosphorylation at the DAPK1 ser308 site.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Cardiopulmonary Resuscitation ; Autophagy/drug effects* ; Heart Arrest/therapy* ; Death-Associated Protein Kinases/metabolism* ; Reperfusion Injury/metabolism* ; Disease Models, Animal ; Neuroprotective Agents/pharmacology* ; Brain Ischemia/metabolism*

ObjectiveTo study the changing law of appearance color and physicochemical properties of Angelicae Sinensis Radix Carbonisata（ASRC） during the processing by color space method combined with statistical analysis， so as to provide reference for determining the processing endpoint and evaluating the quality of the decoction pieces. MethodsTaking processing time（4， 8， 12， 16 min） and temperature（180， 200， 220， 240 ℃） as factors， ASRC decoction pieces with different processing degrees were prepared in a completely randomized design. Then， the brightness value（L^*）， red-green value（a^*）， yellow-blue value（b^*）， and total chromaticity value （E^*ab） of the decoction pieces were determined by spectrophotometer， the color difference value（ΔE） was calculated， and the data of colorimetric values were analyzed by discriminant analysis. At the same time， the pH， charcoal adsorption， and contents of tannins， 5-hydroxymethylfurfural（5-HMF）， tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide of ASRC with different processing degrees were determined by pH meter， ultraviolet and visible spectrophotometry and ultra-high performance liquid chromatography（UPLC）. Principal component analysis（PCA） was used to analyze the data of physicochemical indexes， after determining the processing technology of ASRC， the canonical discriminant function was established to distinguish the decoction pieces with different processing degrees， and leave-one-out cross validation was conducted. Finally， Pearson correlation analysis was used to explore the correlation between various physicochemical indexes and chromaticity values. ResultsWith the prolongation of the processing time， L^*， a^*， b^* and E^*ab all showed a decreasing trend， and the established discriminant model based on color parameters was able to distinguish ASRC with different processing degrees. The pH showed an increasing trend with the prolongation of processing time， and the charcoal adsorption， and the contents of tannins， 5-HMF， and tryptophan all showed an increasing and then decreasing trend. Among them， the charcoal adsorption， contents of tannin and 5-HMF reached their maximum values successively after processing for 8-12 min. While the contents of chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide decreased with the increase of processing time， with a decrease of 60%-80% at 8 min of processing. Therefore， the optimal processing time should be determined to be 8-12 min. PCA could clearly distinguish ASRC with different processing degrees， while temperature had no significant effect on the processing degree. The 12 batches of process validation results（10 min， 180-240 ℃） showed that except for 3 batches identified as class Ⅱ light charcoal， all other batches were identified as class Ⅲ standard charcoal， and the chromaticity values of each batch of ASRC were within the reference range of class Ⅱ-Ⅲ sample chromaticity values. The correlation analysis showed that the chromaticity values were negatively correlated with pH and charcoal adsorption， and positively correlated with contents of tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H， and ligustilide. And both pH and charcoal adsorption were negatively correlated with the contents of the above components， but the charcoal adsorption was positively correlated with the content of 5-HMF. ConclusionThe chromaticity values and the contents of various physicochemical indicators of ASRC undergo significant changes with the prolongation of processing time， and there is a general correlation between chromaticity values and various physicochemical indicators. Based on the changes in color and physicochemical indicators， the optimal processing time for ASRC is determined to be 8-12 min. This study reveals the dynamic changes of the relevant indexes in the processing of ASRC， which can provide a reference for the discrimination of the processing degree and the quantitative study of the processing endpoint.

Objective To explore the correlation between central venous oxygen saturation(ScvO2)-re-lated indexes at different time points and the occurrence of low cardiac output syndrome(LCOS)after con-genital heart disease(CHD)correction surgery.Methods A total of 73 children who underwent CHD correc-tion surgery in this hospital from July 1st,2021 to July 1st,2024 were selected as the research subjects.The clinical data,preoperative conditions,and postoperative conditions of the children were collected.The ScvO2 and arterial lactate(Lac)levels of the children at different time points(the 1st,6th,12th,and 24th hours after surgery)were monitored,and the ScvO2/Lac at different time points and the change rate of ScvO2 in different time periods were calculated.The correlation between ScvO2-related indexes and LCOS after CHD correction surgery was analyzed.Results ScvO2 at the 6th hour after surgery,ScvO2 at the 12th hour after surgery,Sc-vO2/Lac at the 12th hour after surgery,the change rate of ScvO2 from the 1st to the 24th hour after surgery,the change rate of ScvO2 from the 6th to the 12th hour after surgery,and the change rate of ScvO2 from the 12th to the 24th hour after surgery were independent influencing factors of LCOS occurrence after CHD cor-rection surgery(P＜0.05).There was a negative correlation between ScvO2 at the 12th hour after surgery,ScvO2/Lac and LCOS occurrence after CHD correction surgery(r=-0.543,-0.523,P＜0.05).The area under the curve(AUC)of ScvO2 at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.938(95％CI:0.865-1.000);the AUC of ScvO2/Lac at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.922(95％CI:0.851-0.994).Conclusion ScvO2 and ScvO2/Lac at the 12th hour after surgery have good predictive potential for LCOS occurrence af-ter CHD correction surgery.

Objective:To evaluate the morphological and functional changes of the heart during second trimester fetuses with ventricular septal defect (VSD) using fetal heart quantification (fetal HQ) technology.Methods:A prospective study was conducted from July 2022 to January 2024 at Chengdu Women′s and Children′s Central Hospital, collecting 91 singleton fetuses diagnosed with isolated VSD (VSD group) and 91 normal fetuses matched for gestational age (control group). Fetal HQ technology was used to measure the length and width of the four-chamber view of the fetal heart, obtaining the global sphericity index (GSI). Speckle tracking technology was used to track the endocardial motion trajectories of the left and right ventricles during diastole and systole, obtaining parameters such as left and right ventricular global longitudinal strain (LV-GLS and RV-GLS), end-diastolic diameter (EDD), 24-segment sphericity index (SI), 24-segment fraction of shortening (FS), left ventricular ejection fraction (LV-EF), fraction of area change (FAC), left ventricular stroke volume (LV-SV), and left ventricular cardiac output (LV-CO).The differences between groups were compared, and the correlations between the values of VSD and GSI, GLS, and FAC were evaluated.Results:The EDD of the left ventricular segments 20-23 in the VSD group was lower, while the SI value of the right ventricular segments 1-4 in the VSD group was higher than that in the control group (all P<0.05). There was no statistically significant difference in GSI between the two groups ( P>0.05). LV-GLS in the VSD group was lower than that in the control group ( P<0.05). There was no statistically significant difference in RV-GLS ( P>0.05). Values of LV-FAC, LV-EF, LV-SV, and LV-CO in the VSD group were significantly lower than those in the control group (all P<0.05). The FS value of left ventricular segments 1-10 in the VSD group presented lower, but the FS value of right ventricular segments 7-21 higher compared to controls(all P<0.05). LV-GLS and LV-FAC absolute values were negatively correlated with the size of VSD ( r=-0.309, P=0.004; r=-0.264, P=0.015), while GSI, RV-GLS, and RV-FAC showed no significant correlation with the size of VSD (all P>0.05). Conclusions:The overall sphericity index of second trimester VSD fetuses is normal, but there are changes in the shape of the left ventricular apical segments and the right ventricular basal segments, with the left heart chamber tending to be flatter and the right heart chamber more fusiform. The left ventricular systolic function of VSD fetuses is significantly reduced, the local systolic function of right ventricular increases while the global systolic function shows no significant change. The absolute values of LV-GLS and LV-FAC in VSD fetuses are negatively correlated with the size of VSD.

Objective:To summarize the ultrasonographic features and prognosis of fetal persistent vitelline artery.Methods:The prenatal ultrasound features, genetic testing results, and prognosis of a fetus with an isolated persistent vitelline artery that was diagnosed in our hospital in December 2021 were retrospectively analyzed. Relevant articles were retrieved from CNKI, VIP, Wanfang, Yiigle, PubMed, Embase, and UpToDate databases using the terms "persistent vitelline artery", "type Ⅱ single umbilical artery", and "prenatal ultrasound" in both Chinese and English. Prenatal ultrasound features and prognosis of the persistent vitelline artery in fetuses were summarized using descriptive statistical analysis.Results:(1) Case report: In this case, ultrasound at 23 gestational weeks showed that an abnormally large blood vessel deriving from the celiac artery near the superior mesenteric artery entered the placenta through the umbilical opening in parallel with the umbilical vein. Color Doppler showed a blood flow spectrum like that in the umbilical artery. The transverse section image showed that bilateral umbilical arteries were not observed in the bladder and the free segment of the umbilical cord was in the shape of the Chinese character "Lyu". No obvious other structural abnormalities and a negative result of genetic testing were observed in the fetus. Followed up to one year old, the patient showed normal growth and development. (2) Literature review: A total of five articles involving four cases were retrieved (three in English and two in Chinese). Among the five cases, including the present case, one was terminated due to left renal agenesis and abnormal heart arteries ratio revealed by prenatal ultrasound, and the remaining four cases without obvious structural abnormalities in the prenatal ultrasound were born and developed well. Histopathological examination of the umbilical cord was performed in three cases, of which two with persistent vitelline artery had a distinct internal elastic lamina, and one with remained vitelline duct.Conclusions:The prenatal ultrasound of fetal persistent vitelline artery is typically characterized by an abnormal vessel that is derived from the abdominal aorta or superior mesenteric artery and plays the function of the umbilical artery. The prognosis of the isolated persistent vitelline artery is good, but a better understanding of such embryonic abnormalities is needed as there are few relevant reports at home and abroad.

Objective:To analyze the fetal ultrasonographic features of malformation of cortical development (MCD) during the second trimester, and explore and summarize the relevant diagnostic clues, so as to improve the ability of diagnosis and differential diagnosis of fetal MCD.Methods:A total of 313 fetuses with brain abnormalities suspected on ultrasound in Chengdu Women′s and Children′s Central Hospital from April 2018 to August 2022 were retrospectively analyzed. The fetuses were examined using MRI. The ultrasonographic characteristics of fetal MCD were summarized, and the fetal ultrasound and MRI imaging data were compared for fetal MCD.Results:Nineteen fetuses were diagnosed with MCD from 313 fetuses(6.07%, 19/313). Seventeen cases of MCD were identified by ultrasonography and subsequently validated by fetal MRI, including 6 cases of schizencephaly, 2 cases of hemimegalencephaly(HMEG), 3 cases of periventricular nodular heterotopia(PVNH), 3 cases of lissencephaly, 2 cases of microcephaly and 1 case of polymicrogyria(PMG). There were 3 cases with two concurrent MCD, 1 case of HMEG, and MRI increased the diagnosis of left parietal PMG; 1 case of lissencephaly, and MRI increased the diagnosis of PVNH. The other case was PMG, and MRI increased the diagnosis of lissencephaly. Two cases of fetal MCD were not indicated by ultrasonography, one of which was diagnosed as tuberous sclerosis and another one as schizencephaly by MRI, both due to ventriculomegaly.Conclusions:Various types of MCD in the second trimester have ultrasonographic characteristics. Abnormal lateral ventricles, intracranial structural changes such as sulci and gyrus can provide reliable ultrasound diagnostic clues for fetal MCD.

Objective:To study the ultrasonographic characteristics of embryos/fetuses with normal or abnormal central nervous system (CNS) from 7 to 13 +6 weeks of gestation using high resolution two-dimensional ultrasound combined with HD-live silhouette technology and provide a reference for early diagnosis of CNS abnormalities. Methods:Eighty normal embryos/fetuses during 7-13 +6 weeks and 41 fetuses with CNS malformations in early pregnancy during 11-13 +6 weeks were selected to observe the ultrasonographic features of embryos/fetuses with normal or abnormal CNS using transvaginal high resolution two-dimensional ultrasound and HD-live silhouette technology. Descriptive analysis was performed on the results. Results:From seven weeks of gestational age, high resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically show the prosencephalon, mesencephalon and rhombencephalon. The rhombencephalon changed the most in the brain development of embryos. At nine weeks of gestation, cleared structures of pons curvature, the fourth ventricle and cisterna magna were observed. The developing cerebellum and the original Blake pouch cyst were seen at 10 weeks of gestation. From 11 to 13 +6 weeks, the most remarkable change was the choroid plexus of the fourth ventricle changed from perpendicular to parallel to the long axis of the neural tube. Of the 41 fetuses with CNS malformation, 16 (39.0%) were exencephaly, 11 (26.8%) were holoprosencephaly, five (12.2%) were encephalocele, four (9.7%) were anencephaly, three (7.3%) were fourth ventricle dilatation, and two (4.9%) were open spina bifida. Conclusions:High resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically display the morphological changes in embryonic embryos/fetuses with development of normal CNS at 7-13 +6 weeks, which is helpful to better understand the origin of CNS embryonic abnormalities and provide diagnostic clues for the early detection of CNS abnormalities.

In February, 2019, a patient with a defect of open dorsal cartilage and bone in the first metatarsal head, including the defects of soft tissue, tendon and joint capsule, was treated in our department. After multiple debridement, the vascularised medial femoral condyle osteochondral chimeric tissue flap was transferred to repair the composite tissue defect in the metatarsal head at the second stage. After 18 months of follow-up, the patient felt no pain in the foot and walking, and there was no sign of lameness and discomfort at donor sites. The postoperative functional recovery was satisfactory.

Objective To summarize the prenatal ultrasonographic characteristics of anomalous origin of one pulmonary artery from the aorta( AOPA ) ,and describe the diagnostic and clinical outcomes of fetal AOPA . Methods Echocardiographic characteristics of 3 fetuses with AOPA were reviewed . The ultrasonographic features were comparatively analyzed with postpartum autopsy findings . The relevant literature were reviewed and the experience of prenatal diagnosis of AOPA were summarized . Results In 3 cases with AOPA ,2 cases were the proximal type and anomalous origin of right pulmonary artery from the aorta ,of them ,one was accompanied with coarctation of the aorta , the other was accompanied with aortopulmonary window . One case was the distal type and anomalous origin of left pulmonary artery from the left innominate aorta ,it was only associated with mirror right aortic arch and right ductus arteriosus . Ultrasound characteristics were no bifurcation in distal pulmonary artery ,main trunk of pulmonary artery extends directly to one branch ,the other branch originated from the ascending aorta or left innominate artery . Three cases were confirmed by postpartum autopsy . Conclusions There are some characteristic signs on ultrasonic features of AOPA . Prenatal ultrasound has important value for diagnosis of AOPA .

Objective To understand the rationality and safety of oral antihypertensive drugs on chronic renal disease(CKD)combined with hypertension hospitalized patients. Methods It was a multi-center and retrospective investigation. The electronic medical records of CKD with hypertension patients who were hospitalized in 6 comprehensive hospitals in Beijing and used oral antihypertensive drugs on October 1st,2013 to March 31st,2015 were collected. The pharmacists who participated in the project from the 6 research centers filled out the investigation form. According to the drug instruction,the rationality of antihypertensive medication was evaluated by daily dose,frequency of drug delivery,the dosage for renal insufficiency,contraindications and adverse interactions. Results There were 2 833 valid cases in this study,1 730 males and 1 103 females. The ratio of male to female was 1:0.64. The range of age was 18~101 years. The average age was(61 ± 18)years. There were 1 630(57.54%)cases whose age was≥60;314(11.1%)cases were CKD level 1,526(18.6%)cases were CKD level 2,1 117(39.4%)cases were CKD level 3,423(14.9%)cases were CKD level 4,453(16.0%)cases were CKD level 5. 144 (5.1%)cases were hypertension level 1,592(20.9%)cases were hypertension level 2,1 398 cases (49.3%)were hypertension level 3,and 699(24.7%)cases were not graded. The oral hypotensive drugs applied during the hospitalization of 2 833 patients included calcium channel blockers(CCB),beta blockers,diuretics,angiotensin Ⅱ receptor blocker(ARB),angiotensin converting enzyme inhibitors (ACEI),alpha/beta blockers and alpha blockers. 1 022(36.1%)cases used 1 kind of antihypertensive drugs,1 032(36.4%)cases used 2 kinds of antihypertensive drugs,591(20.9%)cases used 3 kinds of antihyper-tensive drugs,157(5.5%)cases used 4 kinds of antihypertensive drugs and 31(1.1%)cases used 5 kinds of antihypertensive drugs. A total of 6038 cases of antihypertensive drugs were administered. The top priority was CCB(35.11%,2 120),the second was beta blockers(17.26%,1 042)and the third was diuretics(16.23%,980). The choice of a single drug for antihypertensive drugs was reasonable. The 2,3,4,5 combined drug users who were not recommended by the guidelines were 4.8%(50/1 032), 21.2%(125/591),28.0%(44/157)and 64.5%(20/31)respectively. The situation of blood pressure control was evaluated with blood pressure target values achieved rate. With blood pressure below 130/80 mmHg as the standard,the admission and discharge blood pressure target achieved rate was 31.2%(884/2 833)and 29.5%(799/2 705)respectively. With blood pressure below 140/90 mmHg as the standard, the admission and discharge blood pressure target achievement rate was 53.6%(1 519/2 833)and 64.4%(1 743/2 705)respectively. Among the 2 833 cases,903(31.9%)cases had 1 204 times of unreasonable use of the drug. The top three were excessive daily frequency of medication(1 029,85.5%),total daily dosage(114,9.5%),and use of drugs that were contraindicated(51,4.2%). Two cases had adverse drug reactions related to antihypertensive drugs. Conclusion The use of antihypertensive drugs in patients with CKD in the six hospitals involved in the investigation was reasonable,but there was still some problems in the combination of drugs. Some doctors are not familiar with the drug instructions,and there are some problems such as increasing the frequency of drug use,overdose medication,and use of drugs that are contraindicated. Clinical pharmacists should be more involved in clinical work in these areas.