Value of machine learning models based on structural MRI for diagnosis of Parkinson disease / 中华放射学杂志

Objective:To explore the value of machine learning models based on multiple structural MRI features for diagnosis of Parkinson disease (PD).Methods:The clinical and imaging data of 60 PD patients (PD group) diagnosed in the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2017 to August 2019 and 56 normal elderly people (NC group) recruited from the community were retrospectively analyzed. All subjects underwent brain MR imaging. Multiple structural MRI features were extracted from cerebellum, deep nuclei and of brain cortex based on different partition templates. The Mann-Whitney U test, as well as least absolute shrinkage and selection operator regression were used to select the most discriminating features. Finally, logistic regression (LR) and linear discriminant analysis (LDA) classifier combined with the 5-fold cross-validation scheme were used to construct the models based on structural features of cerebellum, deep nuclei and cortex, and a combined model based on all features. The receiver operating characteristic curves were drawn, and the diagnostic performance and clinical net benefit of each model were evaluated by the area under curve (AUC) and the decision curve analysis (DCA). Results:In total, four cerebellum (asymmetry index of Lobule Ⅵ volume, asymmetry index of Lobule ⅦB cortical thickness, asymmetry index of total gray matter volume and absolute value of right Lobule Ⅵ gray matter volume), 3 deep nuclei (absolute value of right nucleus accumbens volume, absolute and relative value of total nucleus accumbens volume) and 3 cortex features (local gyration index of left PFm, local fractal dimension of right superior frontal gyrus and sulcal depth of left superior occipital gyrus) were selected as the most discriminating features, and the related models were constructed. In validation set, the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LR classifier were 0.692, 0.641, 0.747 and 0.816; the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LDA classifier were 0.726, 0.610, 0.752 and 0.818. The diagnostic efficiency of the combined models based on LR and LDA classifiers were significantly better than those of other models ( P<0.05). The DCA curve demonstrated that the combined models based on LR and LDA classifiers showed the highest clinical net benefit. Conclusion:The combined models with all structural features of cerebellum, deep nuclei and cortex included based on LR and LDA classifiers showed favorable performance and clinical net benefit for diagnosis of PD, which have the potential application value in clinical diagnosis.

The protective effect of L-Shikonin on LPS/D-GalN-induced acute liver injury in mice via inhibiting NF-κB inflammatory signaling pathway / 中国药理学通报

Aim To investigate the anti-inflammatory effect of L-Shikonin ( SK ) on lipopolysaccharide ( LPS)-induced RAW 264. 7 macrophages in vitro and its protective effect on LPS/D-GalN-induced acute liver injury. Methods The mouse model of acute liver in¬jury was established in vivo experiments by LPS/D- GalN. The survival rate of the mice and the changes of liver and spleen indices in each group were examined. The levels of AST, ALT and AKP in serum and NO, superoxide dismutase ( SOD ) and malondialdehyde (MDA) in liver tissue homogenate were measured, and the histopathological sections of the liver of each group were observed by H&E staining. M I T colorimet- ric assay was used for cell viability in vitro experi¬ments, Griess method for the detection of NO content, RT-PCR assay and Western blot assay for examining the effect of levulinic acid on the expression levels of mRNA and related pathway proteins of pro-inflammato¬ry factors in LPS-induced RAW264. 7 cells. Results The results of in vivo experiments showed that L-SK significantly improved the liver and spleen indices, de¬creased AST, ALT and AKP levels in serum, de¬creased NO and MDA in liver homogenate, and in¬creased SOD activity in mice with acute liver injury. The results of in vitro experiments showed that L-SK significantly inhibited the mRNA expression of INOS, COX2, I FN-(3 and pro-inflammatory factors 1L-6, TNF-a and IL-10 in LPS-induced RAW264. 7 cells, and significantly inhibited the protein expression of IN¬OS, COX2 and the NF-kB signaling pathway. Conclu¬sions L-SK has good anti-inflammatory effects in LPS-induced inflammation in RAW 264. 7 cells in vitro. Il inhibits the protein expression of phosphorylated P65 and IKKaαβ in the NF-kB signaling pathway, thereby suppressing the anti-inflammatory effects in vitro and L- Shikonin has protective effects against acute liver injury in mice.

Anesthesia management for resection of adrenal cortical carcinoma in children / 中华麻醉学杂志

The medical records of 11 pediatric patients undergoing resection of adrenal cortical carcinoma from January 2012 to January 2019 in our hospital were collected.Anesthesia management for resection of adrenal cortical carcinoma in children was analyzed and investigated.Anesthesia was induced by intravenously injecting atropine 0.01 mg/kg, dexamethasone 2-5 mg, propofol 2-3 mg/kg, sufentanil 0.3-0.5 μg/kg or fentanyl 1-2 μg/kg, rocuronium 0.5 mg/kg or cis-atracurium 0.1-0.2 mg/kg.Radial artery catheterization and femoral vein catheterization were performed under ultrasound guidance.Arterial blood pressure was continuously monitored.The esophageal thermometers probe was placed to continuously monitor body temperature.The catheter was placed to monitor urine volume.Intermittent positive pressure ventilation was performed after endotracheal intubation with the inspiratory oxygen fraction set 60%-100%, oxygen flow rate 2-3 L/min, tidal volume 7-10 ml/kg, ventilation frequency 20-26 times/min, inhalation/respiration ratio 1∶(1.5-2.0) and airway pressure 16-20 cmH 2O, and the end-tidal pressure of carbon dioxide was maintained at 35-45 mmHg.Anesthesia was maintained by inhaling 2%-4% sevoflurane and/or intravenously infusing propofol 0.10-0.15 mg·kg -1·min -1, and continuously infusing remifentanil 0.2-0.5 μg·kg -1·min -1.Hemodynamics was maintained within the normal range, and the bispectral index was maintained at 40-60 during the surgery.Before the tumor was completely removed, 5-10 mg/kg sodium hydrocortisone succinate was intravenously infused.At the end of the operation, sufentanil 0.75-1.00 μg·kg -1·d -1 or fentanyl 7.5-10.0 μg·kg -1·d -1 was continuously infused for postoperative analgesia until 48 h after operation.Operation was smoothly completed with stable anesthesia in all the pediatric patients.The tracheal tube was removed successfully after the operation.All children in this group were discharged from hospital and no death occurred.Anesthesia management for resection of adrenal cortical carcinoma required an appreciation of the clinical characteristics and perioperative pathophysiological changes.Paying attention to the changes in hormone levels during perioperative period and timely adjusting the children′s internal environment to maintain the stability of anesthesia and reduce the stress response were the keys to anesthesia management.

Progress in the 16S rRNA Gene Sequencing in Forensic Science / 法医学杂志

Forensic microorganism is one of the hotspots of forensic science research. Due to its conservatism and specificity, the 16S rRNA gene is found to be an ideal marker for forensic identification. With the rapid development of high throughput sequencing technology, the research on microorganisms has been gradually applied to many fields such as environment and health care. In the field of forensic science, the results of forensic microbiology research, represented by 16S rRNA gene sequencing, are also gradually applied to forensic practice, such as biological samples identification, individual identification, postmortem interval estimation, and regional inference, which not only provide clues for the investigation of cases but also complement and assist traditional methods. This paper describes the research methods and related sequencing technologies of 16S rRNA gene sequencing, summarizes its research progress, and discusses the application value and potential of 16S rRNA in forensic science.

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.</p><p><b>METHODS</b>Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.</p><p><b>RESULTS</b>Compared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.</p>

Research Progress on Gene Alterations of Amelogenin Locus in Gender Identification / 法医学杂志

There are two kinds of amelogenin gene mutation, including mutation in primer-binding region of amelogenin gene and micro deletion of Y chromosome encompassing amelogenin gene, and the latter is more common. The mechanisms of mutation in primer-binding region of amelogenin gene is nucleotide point mutation and the mechanism of micro deletion of Y chromosome encompassing amelogenin gene maybe non-allelic homologous recombination or non-homologous end-joining. Among the population worldwide, there is a notably higher frequency of amelogenin gene mutations in Indian population, Sri Lanka population and Nepalese population which reside within the Indian subcontinent. Though amelogenin gene mutations have little impact on fertility and phenotype, they might cause incorrect result in gender identification. Using composite-amplification kit which including autosomal STR locus, amelogenin gene locus and multiple Y-STR locus, could avoid wrong gender identification caused by amelogenin gene mutation.

Identification of Vaginal Fluid Using Microbial Signatures / 法医学杂志

OBJECTIVES@#To investigate the specific microbial signatures in vaginal fluid.@*METHODS@#Vaginal fluid （16 samples）, saliva （16 samples）, feces （16 samples）, semen （8 samples）, peripheral blood （8 samples）, urine （5 samples）, and nasal secretion （4 samples） were collected respectively. The 16S rRNA genes of Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus iners, and Atopobium vaginae were amplified. PCR production was detected via a 3130xl Genetic Analyzer.@*RESULTS@#The detected number of Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus iners, and Atopobium vaginae were 15, 5, 8, 14, and 3 in all vaginal fluid samples, respectively. Lactobacillus crispatus and Lactobacillus jensenii existed specifically in vaginal fluid.@*CONCLUSIONS@#There is a potential application value to detect Lactobacillus crispatus and Lactobacillus jensenii for the identification of vaginal fluid.

Source Identification of Human Biological Materials and Its Prospect in Forensic Science / 法医学杂志

Source identification of human biological materials in crime scene plays an important role in reconstructing the crime process. Searching specific genetic markers to identify the source of different human biological materials is the emphasis and difficulty of the research work of legal medical experts in recent years. This paper reviews the genetic markers which are used for identifying the source of human biological materials and studied widely, such as DNA methylation, mRNA, microRNA, microflora and protein, etc. By comparing the principles and methods of source identification of human biological materials using different kinds of genetic markers, different source of human biological material owns suitable marker types and can be identified by detecting single genetic marker or combined multiple genetic markers. Though there is no uniform standard and method for identifying the source of human biological materials in forensic laboratories at present, the research and development of a series of mature and reliable methods for distinguishing different human biological materials play the role as forensic evidence which will be the future development direction.

Protective effect of adiponectin on glucose and lipid metabolism by sup-pressing MHCⅡexpression / 中国病理生理杂志

AIM:To investigate whether the protective effect of adiponectin on glucose and lipid metabolism is achieved through down-regulating major histocompatibility complex classⅡ( MHCⅡ) in the adipose tissue.METHODS:Adiponectin knockout ( KO) mice and C57BL/6 ( WT) mice were fed with high-fat diet and standard diet for 24 weeks, re-spectively.The body weight, fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insu-lin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol ( HDL-C) , hepatic histology, and classⅡtrans-activator ( CIITA) , histocompatibility 2 class II antigen E beta (H2-Eb1) and cluster of differentiation 74 (CD74) mRNA and MHC II protein levels in adipose tissue were measured at sacrifice.siRNA targeting MHC II and overexpression vector was used in 3T3-L1 cells to explore the effect of adiponectin on the protein level of MHCⅡ.RESULTS:The levels of body weight, FBG, FINS, HOMA-IR, TC, TG, LDL-C, hepatic steatosis, CIITA, H2-Eb1 and CD74 mRNA expression, and MHCⅡ protein expression in the KO mice were higher than those in the WT mice that fed with high-fat diet or standard diet.In 3T3-L1 cells, inhibition of adiponectin reversed MHC II protein level induced by specific siRNA.The expression of MHC II in adipocytes decreased after adiponectin was overexpressed.CONCLUSION: Adiponectin improves glucose and lipid metabolism through sup-pressing the expression of MHCⅡin the adipose tissue.

Application of Ion Torrent PGM™ System in Detection of Fetal DNA in Maternal Plasma / 法医学杂志

OBJECTIVE@#To explore the feasibility of detecting of Y-STR of fetal DNA in maternal plasma using Ion Torrent PGM™ System.@*METHODS@#A total of 16 fetal DNA samples from maternal plasmas (8 cases from 38 weeks gestational age and 8 ones from 12 weeks) were prepared and a multiplex assay with 7 STR loci (DYS390, DYS391, DYS393, DYS438, DYS437, DYS456, DYS635) was designed for multiplex-PCR amplification. Using Ion Torrent PGM™ System, the results of Y-STR sequences and capillary electrophoresis were obtained and compared.@*RESULTS@#Y-STR specific alleles were detected in the maternal plasma of all the pregnant women having male babies of second and third trimester, which were higher than that detected by capillary electrophoresis. Consistent Y-STR genotypes were observed between fetal DNA from maternal plasma and genomic DNA from the newborn babies.@*CONCLUSION@#Based on Ion Torrent PGM™ System, the prenatal Y-STR detection method may provide a high-sensitive and high-throughput choice for prenatal STR detection in forensic testing.

Determination of the biological attribute of evidence at the scene using reverse transcription PCR and real-time fluorescent quantitative PCR / 法医学杂志

OBJECTIVE@#To explore the feasibility of biological method to identify the biological attribute of samples at crime scene.@*METHODS@#Thirty samples of ten blood stains, ten saliva stains and ten semen stains were selected, and all the samples were processed by the routine method and biomolecular method, respectively. Both RNA and DNA were isolated using DNA-RNA co-extraction technology and the mRNA was converted into cDNA using reverse transcription PCR (RT-PCR). Three pairs of specific primers were designed for blood stain, saliva stain and semen stain based on the different target genes in three specific tissues and the primers were amplified using real-time fluorescent quantitative PCR. The differences in these biological samples were evaluated by melting temperature (Tm) values and the size of the amplification fragment.@*RESULTS@#The Tm values of blood stain, saliva stain and semen stain were (84.5 +/- 0.2) degrees C, (76.9 +/- 0.3) degrees C and (88.5 +/- 0.2) degrees C, respectively. The length of PCR fragments of them was 177bp, 134bp and 294bp, respectively.@*CONCLUSION@#Compared with the routine method, RT-PCR with real-time fluorescent quantitative PCR is highly specific, sensitive and reliable to identify the biological attribute of evidence, and can be potentially applied to determine evidence attribute in forensic practice.

Forensic application of expressmarker 22 STR loci direct PCR amplification kit / 法医学杂志

OBJECTIVE@#To explore the application value of Expressmarker 22 STR loci direct PCR amplification kit.@*METHODS@#One thousand nine hundred and forty-eight samples (including samples spotted on FTA cards, filter papers and case samples) were tested using Expressmarker 22 STR loci direct PCR amplification kit. At the same time, all were tested using Sinofiler kit, Identifiler kit and PowerPlex 16 kit respectively for comparison. The genotypes were compared at the same STR loci among these four kits to test the sensitivity and accuracy of Expressmarker 22 STR loci direct PCR amplification kit.@*RESULTS@#97.79% samples were successfully typed using Expressmarker 22 STR loci direct PCR amplification kit. The genotype profiles of the same samples using Expressmarker 22 STR loci direct PCR amplification kit were consistent with Sinofiler kit, Identifiler kit and PowerPlex 16 kit at the same STR loci.@*CONCLUSION@#Expressmarker 22 STR loci direct PCR amplification kit can provide huge information and accurate results

Effect of adenovirus-mediated local tissue factor pathway inhibitor gene transfer on thrombosis formation in rabbit carotid artery injuries / 中国地方病学杂志

Objective To observe the effects of tissue factor pathway inhibitor(TFPI) on thrombosis formation in rabbit carotid arteries after ballon injury. Methods Fouty rabbits with the weight 2.5-3.0 kg were respectively divided into 4 groups, Ad-TFPI, Ad-LacZ, PBS and normal control groups. The normal control group was not given any treatment and other 3 groups were given 0.2 ml Ad-TFPI, Ad-LacZ or PBS reproduced by the Dispatch catheter respectively after the PTCA balloon iniury on the right carotid arteries. Ten days after gene transfer the repeated balloon injury was performed in the 3 groups, and the first balloon injury was performed in the normal control group by the same method. The carotid blood flow was recovered immediately after the injury. Thirty minutes later all the animals were sacrificed. The injured carotid arteries and one part of contralateral normal artery were cut down, scissored along the long axis, flattened and fixed in the 2% glutaral. The platelet aggregation and thrombosis formation on the luminal surfaces was observed under electron microscope. Results The electron microscope results showed that the vascular endothelial cell structure was integrated and lined up in order in the nomal artery which had no any injury. After the balloon injury in the normal control group, the structure of the endothelial cell was disintegrated, and there was some platelet aggregation but no fibrosis formation. A large amount of platelet aggregated but no fibrosis formed in Ad-TFPI group after the repeated balloon injury. A large amount of fibrosis formed and red cells piled up in the Ad-LacZ and PBS group. The positive rate of thrombosis formation among groups had siginificant differences(χ2=14.95, P<0.01). The positive rate in Ad-TFPI group(20%) was lower than that in Ad-LacZ group(80%, χ2=7.20, P<0.01) and PBS group(70%, χ2=5.05, P<0.05), but was higher than that in the normal control group(10%, χ2=0.39, P>0.05). The positive rate in Ad-LacZ group(80%) was higher than in the normal control group(10%, χ2=9.90, P<0.01) and in the PBS group(70%, χ2=0.27, P> 0.05). The positive rate in PBS group(70%) was higher than that in the normal control group(10%, χ2=7.50, P< 0.01). Conclusions The repeated balloon injury method can cause a large amount of fibrosis formation in the rabbit carotid. TFPI gene inhibits thrombosis formation in balloon-injured rabbit carotid arteries.

Ad-TFPI gene transfer attenuates intimal proliferation in rabbit carotid arteries after balloon injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the in vivo gene expression of adenovirus-mediated human tissue factor pathway inhibitor (hTFPI) and its inhibition effects on intimal proliferation in rabbit carotid arteries after balloon injury.</p><p><b>METHODS</b>Rabbits underwent carotid artery balloon injuries were treated with Ad-TFPI (n = 25), Ad-LacZ (n = 25) or PBS (n = 10), respectively. Sham operated rabbits (n = 10) serve as normal controls. The expressions of human TFPI at mRNA and protein levels were detected by RT-PCR and ELISA respectively on the 3rd, 7th, 10th, 14th, 28th day after operation. Intimal proliferation was detected by angiograms and morphometric analysis.</p><p><b>RESULTS</b>TFPI mRNA and protein expressions were detected at 3 days and peaked at the 10th and 14th day after TFPI gene transfer. The expressions were still detectable on the 28th day. There was no TFPI expression in Ad-LacZ group. The carotid angiogram results indicated that the minimal lumen diameter in TFPI group was significantly larger and the lumina stenosis percentage was significantly lower in TFPI group compared those in Ad-LacZ and PBS groups (all P < 0.05). The morphometric analysis showed that the intimal area, the ratio of the intimal/media area, the lumina stenosis percentage in TFPI group were all significantly reduced compared with those in Ad-LacZ and PBS groups (all P < 0.01).</p><p><b>CONCLUSIONS</b>The TFPI gene could be effectively transferred by adenovirus vector to injured carotid arteries and transferred Ad-TFPI could significantly attenuate intimal proliferation in balloon injured carotid arteries in rabbits.</p>