3D hippocampal segmentation based on spatial and frequency domain features adaptive fusion and inter⁃class boundary region enhancement / 解剖学报

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Quantitative Analysis of Multi-components in Gnaphalium affine Based on UPLC-Q-Exactive Orbitrap MS / 中国实验方剂学杂志

ObjectiveTo establish a rapid and stable liquid chromatography-mass spectrometry（LC-MS） for simultaneous analysis of 17 chemical components in Gnaphalium affine aboveground parts with flowers， so as to provide experimental basis for improving the quality standard of this herb. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used for the quantitative analysis of 17 constituents in 15 batches of G. affine from different origins， the separation was performed on an ACQUITY UPLC® BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of methanol（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-1.0 min， 8%A； 1.0-4.0 min， 8%-26%A； 4.0-9.0 min， 26%A； 9.0-14.0 min， 26%-34%A； 14.0-14.5 min， 34%-45%A； 14.5-15.0 min， 45%-60%A； 15.0-18.0 min， 60%-90%A； 18.0-19.0 min， 90%A； 19.0-19.01 min， 90%-8%A； 19.01-20.0 min， 8%A）， the flow rate was 0.3 mL·min-1， the column temperature was 40 ℃ and the injection volume was 2 μL. And the electrospray ionization was used with full scanning in both positive and negative ion modes， and the scanning range was m/z 100-1 000. ResultThe established method has been verified by the methodology and could be used for the simultaneous quantification of 17 components in G. affine. The content ranges of the 17 components（quinic acid， gallic acid， protocatechuic acid， neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， caffeic acid， 1，3-O-dicaffeoylquinic acid， isochlorogenic acid A， isoquercitrin， 1，5-O-dicaffeoylquinic acid， apigenin-7-O-glucoside， astragalin， isochlorogenic acid C， luteolin， apigenin and hispidulin） in 15 batches of G. affine samples was 39.60-179.12， 0.17-0.84， 2.41-8.38， 4.33-31.50， 13.63-180.38， 2.43-14.75， 1.16-19.68， 0.49-5.63， 55.77-445.16， 0.23-10.26， 62.04-530.10， 1.11-18.01， 11.36-90.61， 12.22-65.98， 7.22-69.84， 3.37-45.65， 0.30-2.59 μg·g-1， respectively. The content of organic acids was higher than that of flavonoids in G. affine， and the contents of 1，5-O-dicaffeoylquinic acid， isochlorogenic acid A， quinic acid and chlorogenic acid were higher. Meanwhile， the content of flavonoids in the samples from Guizhou was higher than that from Jiangsu， while the content of organic acids in the samples from Jiangsu was higher than that from Guizhou. ConclusionThe established method can be used for the rapid and accurate determination of 17 components in G. affine， which clarifies the content range of the main components in this herb， and can provide a reference for the selection of quality control markers of G. affine.

Analysis of Chemical Components and Tissue Distribution of Lujiao Formula Based on UPLC-Q-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）. MethodThe separation was performed on an ACQUITY UPLC® BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-methanol（B） in a gradient elution（0-2 min， 4%B； 2-6 min 4%-12%B； 6-38 min， 12%-70%B； 38-38.5 min， 70%B； 38.5-39 min， 70%-95%B； 39-43 min， 95%B； 43-43.1 min， 95%-4%B； 43.1-45 min， 4%B）， the flow rate was 0.3 mL·min-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization（ESI） in the full scanning mode of positive and negative ions， the scanning rang was set at m/z 100-1 500， the collision energies were 10， 20， 40 eV. Retention time， precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution， combing with self-established database and comparing with standard substances and published literature data. ResultA total of 260 compounds， including 156 flavonoids， 43 terpenoids， 18 coumarins， 13 organic acids， 7 phenylethanoids， 7 alkaloids and 16 others， were identified or hypothesized from Lujiao formula， 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100， 143， 129 and 126 prototype components were detected in blood， heart， liver and kidney， respectively. ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed， which can provide reference for the quality control， clinical application， pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory / 神经科学通报·英文版

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

Current research status of animal models for acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.

Therapeutic effect of transplantation of bone marrow mesenchymal stem cells co-cultured with bone marrow M2 macrophages on a rat model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSCM2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl4）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSCM2. The rats were given subcutaneous injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSCM2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl4. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSCM2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSCM2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSCM2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl4/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Effect of South African Herb Hoodia gordonii on Liver Glucolipid Metabolism and PI3K/Akt/FoxO1 Signalling Pathway in db/db Mice / 中国实验方剂学杂志

ObjectiveTo observe the effects of the South African herb Hoodia gordonii （HG） on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase （PI3K）/protein kinase B （Akt）/factor forkhead protein O1 （FoxO1） signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose： model group， metformin group （0.195 g·kg-1）， and low dose （0.39 g·kg-1）， medium dose （0.78 g·kg-1）， and high dose （1.56 g·kg-1） HG groups， with six m/m mice in each group， and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg-1 by gavage. Body weight， water intake， and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration， serum insulin （FINS）， low-density lipoprotein cholesterol （LDL）， total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine （CREA） were measured， and liver sections were embedded and stained with hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and oil red O. Protein expression of PI3K p85， p-Akt， and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K， Akt， and FoxO1 in liver tissue was detected by real-time polymerase chain reaction （Real-time PCR）. ResultAfter six weeks of administration intervention， it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups （P<0.05）. The level of islet resistance index was significantly reduced in both the low and medium dose HG groups （P<0.05）. The expression levels of TC， TG， and LDL were reduced in all HG groups （P<0.05， P<0.01）. Pathologically， HG could alleviate hepatocyte steatosis， reduce the volume and content of lipid droplets in liver， and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low， medium， and high dose HG groups compared with the model group （P<0.01）. p-Akt protein expression was significantly increased in the medium and high dose HG groups （P<0.05， P<0.01）. p-FoxO1 protein expression was significantly increased in the low， medium， and high dose HG groups （P<0.05， P<0.01）. Compared with the model group， PI3K mRNA was increased in low dose， medium dose， and high dose HG groups （P<0.05）， and Akt mRNA was increased in high dose HG group （P<0.05）. FoxO1 mRNA was decreased in low dose， medium dose， and high dose HG groups （P<0.05）. ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice， which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples / 中华医学遗传学杂志

OBJECTIVE@#To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies.@*METHODS@#A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups.@*RESULTS@#Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2 = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2 = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2 = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up.@*CONCLUSION@#The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

Retrospective analysis and comparison of total internal disability preservation technique and standardized reconstruction technique / 中国骨伤

OBJECTIVE@#To investigate the efficacy and clinical results of total internal protection technique in anterior cruciate ligament reconstruction.@*METHODS@#A total of 56 patients undergoing anterior cruciate ligament reconstruction treated from January 2018 to December 2019 were selected. According to the different surgical methods, they were divided into total internal reconstruction group and standard bone tunnel group. There were 21 patients in the total internal reconstruction group, including 15 males and 6 females, aged from 20 to 48 with an average of (35.6±6.7) years old, and 35 patients in the standard tibial tunnel group, including 26 males and 9 females, aged 22 to 51 years old with an average of (33.7±9.6) years old. Preoperative examination of Lachman test was positive, magnetic resonance indicated anterior cruciate ligament rupture. There were no significant differences between the two groups in age, sex, body mass index, time from injury to ACL reconstruction, combined meniscus injury and operation method, operation time, ligament diameter, ligament length and other general information. Postoperative evaluation included operation duration, length and diameter of transplanted tendon after braid. International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner score and perioperative complications 2 years after surgery.@*RESULTS@#Both groups were followed up, ranging from 24 to 30 months with an average of (26.9±3.4) months. Postoperative incision healing was good, and no failure or joint infection occurred at the last follow-up. There was no statistically significant difference between the two groups in IKDC score, Lysholm score and Tegner score before, 1 year and 2 years after surgery. However, IKDC score, Lysholm score and Tegner score at 1 year and 2 years after surgery.@*CONCLUSION@#The same postoperative function and stability of knee joint can be obtained by both the residual whole technique and the standardized reconstruction technique. In the residual whole group, only the semitendinosus muscle is taken, and the femoral thin muscle is retained, with greater tibial bone mass preserved, which is safe and effective in clinical practice.

Exploring the protective mechanism of Tibetan medicine Potentilla anserine on cyclophosphamide-induced myelosuppression based on metabonomics technology / 药学学报

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Value of chromosomal microarray analysis for the diagnosis of fetuses with anomalies of central nervous system / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up.@*METHODS@#A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis.@*RESULTS@#In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001).@*CONCLUSION@#Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.

Comparison of detection rates of chromosome G-banding karyotype analysis and fluorescence in situ hybridization among children with sex chromosome mosaicisms / 中华医学遗传学杂志

OBJECTIVE@#To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms.@*METHODS@#A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared.@*RESULTS@#The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05).@*CONCLUSION@#No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.@*METHODS@#Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.@*RESULTS@#A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.@*CONCLUSION@#Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Total flavonoids of Dracocephalum moldavica L. inhibit oxidative stress against H9c2 cell ischemia-reperfusion injury via VEGF-B/AMPK pathway / 药学学报

Total flavonoids of Dracocephalum moldavica L. (TFDM) is an effective component extracted and isolated from the traditional Uighur medicinal herb Cymbidium fragrans. Cymbidium fragrans has the effects of tonifying the heart and brain, promoting blood circulation and resolving blood stasis, and has been widely used in the treatment of cardiovascular and cerebrovascular diseases for a long time. The purpose of this study was to determine the effect of total flavonoids from Cymbidium fragrans on hypoxia/re-oxygenation (H/R) injury in H9c2 (rat cardiomyocytes) cells and its mechanism. A model (H/R) of hypoxia/re-oxygenation injury in H9c2 cells was established using hypoxia and glucose deprivation for 9 h combined with re-oxygenation and rehydration for 2 h to simulate myocardial ischemia-reperfusion injury. The effects of total flavonoids from Cymbidium fragrans on cell viability, markers of myocardial cell damage, oxidative stress levels, and reactive oxygen radical (ROS) content were investigated, Western blot was used to detect the expression of vascular endothelial growth factor B (VEGF-B) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway related proteins. The results showed that the total flavonoids of Cymbidium fragrans significantly increased the viability of myocardial cells after H/R injury, and decreased the content of lactate dehydrogenase (LDH) and creatine kinase isozyme (CK-MB) in the cell supernatant. It significantly reduced malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decreased intracellular ROS and nitric oxide (NO) content. Western blot analysis showed that the total flavonoids of Cymbidium fragrans decreased Bax levels in H9c2 cells damaged by H/R and increased Bcl-2 expression. Total flavones of Cymbidium fragrans upregulate VEGF-B/AMPK pathway related proteins VEGF-B, vascular endothelial growth factor receptor 1 (VEGFR-1), neuropilin 1 (NRP-1), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated adenosine monophosphate activated protein (p-AMPK) and phospho mechanistic target of rapamycin (p-MTOR) levels. The above research results indicate that the total flavonoids of Cymbidium can significantly reduce the H/R injury of myocardial cells, which may be related to the upregulation of VEGF-B/AMPK pathway and inhibition of oxidative stress response.

Analysis and enlightenment of drug-related administrative penalty cases in medical institutions from 2020 to 2022 / 中国药房

OBJECTIVE To analyze the patterns and characteristics of drug-related administrative penalty cases with medical institutions as parties from 2020 to 2022 in order to further improve drug management in medical institutions. METHODS A retrospective statistical analysis was used to summarize the drug-related administrative penalty decisions with medical institutions as parties， and to match them with the provisions of the Drug Administration Law （2019 version） for statistical analysis. RESULTS There were 144 complete administrative penalty decisions with medical institutions as parties. Analyzed by cause， 126 cases of administrative punishment for inferior drugs accounted for 87.50%， of which expired drugs accounted for more than 50.00% of the inferior drug cases； 15 cases （10.42%） were for purchasing drugs from enterprises or individuals not qualified to operate drugs. Analyzed by the range of punishment amount of the cases， 34 cases （23.61%） resulted in lighter penalties， while 81 cases （56.25%） resulted in reduced penalties. CONCLUSIONS There are extremely few medical institutions that have received administrative penalties for drug management violations. Medical institutions should strengthen the awareness of law-abiding， and know the red line of drug management and the illegal behavior that is easy to occur， so as to better strengthen drug quality management.

Buyang Huanwutang Alleviates Inflammatory Injury After Cerebral Ischemia-reperfusion in Rats via Activating Adiponectin Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Buyang Huanwutang （BYWHT） on reducing inflammatory injury and improving neurological function after cerebral ischemia-reperfusion in rats via activating the adiponectin （APN） pathway. MethodMale SD rats were randomized into sham， model， BYHWT （16 g·kg-1， twice a day）， and BYHWT + APN inhibitor （GW9662） groups. In the sham group， blood vessels were isolated. The rat model of middle cerebral artery occlusion （MCAO） was established. The rats in the BYHWT+GW9662 group was treated with subcutaneous injection of GW9662 at 4 m·kg-1 30 min before MCAO surgery and BYHWT at 16 g·kg-1 by gavage after MCAO surgery， once in the morning and once in the evening. The immunofluorescence （IF） assay was employed to observe the expression of adiponectin receptor 1 （AdipoR1） and the colocalization of AdipoR1 with neuronal nuclei （NeuN） and ionized calcium binding adaptor molecule 1 （Iba1） in the brain. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of APN in the serum and brain. The balance beam test was carried out to examine the balance ability， and the grasping test to assess the recovery of limb strength. The immunofluorescence assay was used to detect the expression of myeloperoxidase （MPO）. Western blot was employed to determine the expression of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， IL-6， and IL-10 and in the brain. ResultCompared with the sham group， the modeling promoted the expression of AdipoR1 （P<0.01）， lowered the APN levels in the serum and brain （P<0.05， P<0.01）， increased the score in the balance beam test （P<0.01）， and decreased the grasping strength of forepaw （P<0.01）， which were accompanied with increased MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and decreased IL-10 level （P<0.01）. Compared with the model group， BYHWT promoted the expression of AdipoR1 （P<0.01）， elevated APN levels in the serum and brain （P<0.05， P<0.01）， and increased the grasping strength of forepaw （P<0.01）， which were accompanied with lowered MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and elevated IL-10 level （P<0.01）. All the above effects were partially blocked by GW9662. ConclusionBYHWT can reduce inflammatory injury and improve neurological function in the rat model of cerebral ischemia-reperfusion by activating the APN pathway.

Effect and Mechanism of Yiyi Fuzi Baijiangsan on Apoptosis of Human Colon Cancer HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Yiyi Fuzi Baijiangsan （YYFZBJ） on the apoptosis of colon cancer cell line HCT116. MethodYYFZBJ at different concentrations （0.5， 1， 2， 4， 6， 8， 10， 12， 14， 16 g·L-1） was used to intervene in HCT116 cells for 24， 48， 72 h. The cell counting kit-8 （CCK-8） method was used to determine the effect of YYFZBJ on cell proliferation in vitro. The cells were divided into a blank group， a capecitabine group（1.8 g·L-1）， and low-， medium-， and high-dose YYFZBJ groups （6， 10， and 14 g·L-1） and treated for 48 hours. Flow cytometry was used to detect the apoptosis. Hoechst 33342 staining was used to observe the apoptotic morphology of cells. Mitochondrial membrane potential （MMP） was analyzed by a mitochondrial-targeted deep-red fluorescent probe （Mito-Tracker Red CMXRos）. The expression of proteins related to the mitochondrial apoptosis pathway， such as B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome C （Cyt C）， cysteinyl aspartate-specific protease （Caspase）-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 was detected by Western blot. The mRNA levels of Bcl-2， Bax， Cyt C， Caspase-9， and Caspase-3 were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， YYFZBJ （8， 10， 12， 14， 16 g·L-1） significantly inhibited the proliferation of HCT116 cells in vitro （P<0.05） in a dose-dependent manner. Compared with the blank group， the medium- and high-dose YYFZBJ groups and the capecitabine group showed increased apoptosis rates of colon cancer cells （P<0.05）. The YYFZBJ groups and the capecitabine group showed reduced number of colon cancer cells with significantly changed cellular morphology and cell apoptosis manifestations， such as strong dark blue fluorescence， nucleus concentration， shrinkage， and fragmentation. With the increase in the mass concentration of YYFZBJ， the blue fluorescence intensity was significantly enhanced. Compared with the blank group， the YYFZBJ groups and the capecitabine group showed reduced MMP in a dose-dependent manner， decreased protein and mRNA levels of Bcl-2， and increased protein expression of Bax， Cyt C， Caspase-9， Caspase-3， cleaved Caspase-9， and cleaved Caspase-3 and mRNA expression of Bax， Cyt C， Caspase-9， and Caspase-3 （P<0.05）. ConclusionYYFZBJ can induce the apoptosis of colon cancer HCT116 cells through the mitochondrial apoptosis pathway.