The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. METHODS: A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. RESULTS: Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). CONCLUSION For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.
Female ; Pregnancy ; Humans ; Mosaicism ; In Situ Hybridization, Fluorescence ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Microarray Analysis/methods* ; Chromosomes

Objective:To investigate the correlation between systemic inflammatory response index (SIRI) and the outcomes at 90 d after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke received intravenous thrombolysis in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively enrolled. SIRI was calculated according to neutrophil count, lymphocyte count, and monocyte count at admission. The modified Rankin Scale score was used to evaluate the outcomes at 90 d after onset. 0-2 was defined as good outcome, and 3-6 were defined as poor outcome. Multivariate logistic regression analysis was used to evaluate the independent correlation between SIRI and poor outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI for poor outcomes. Results:A total of 303 patients with acute ischemic stroke receiving intravenous thrombolysis were enrolled in the study, including 178 (58.7%) males. Their median age was 69 years (interquartile range 60-78 years), and 69 patients (22.8%) had poor outcomes. SIRI in the poor outcome group was significantly higher than that in the good outcome group (1.53±2.45 vs. 3.51±4.73; P<0.05). Multivariate logistic regression analysis showed that the National Institutes of Health Stroke Scale (NIHSS) score at admission (odds ratio [ OR] 1.230, 95% confidence interval [ CI] 1.151-1.315; P<0.001) and SIRI ( OR 1.240, 95% CI 1.074-1.432; P=0.003) were significantly associated with the poor outcomes at 90 d. ROC curve analysis showed that the areas under the curve for SIRI and NIHSS scores alone and in combination to predict poor outcomes were 0.721 (95% CI 0.650-0.792; P<0.001), 0.824 (95% CI 0.771-0.878; P<0.001) and 0.853 (95% CI 0.804-0.902; P<0.001), respectively. The best cut-off values were 1.59, 8.00, and 0.23, respectively, and the sensitivity and specificity were 60.9% and 73.9%, 76.8% and 75.6%, 75.4% and 82.5%, respectively. Conclusions:High SIRI at admission is independently associated with 90-day poor outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. SIRI may be used as an outcome predictor in patients undergoing intravenous thrombolysis.

Objective:To analyze the diagnostic value of metabolic makers in cerebrospinal fluid in advanced lung adenocarcinoma patients with leptomeningeal metastases (LM) .Methods:A total of 46 cerebrospinal fluid samples (LM group) from lung adenocarcinoma patients with LM admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from December 2019 to December 2021 were collected, and 48 cerebrospinal fluid samples (control group) from patients with benign neurological diseases during the same period were collected. Metabolomics analysis of cerebrospinal fluid was carried out by high-performance liquid chromatography-mass spectrometry. Principle component analysis (PCA) and orthogonal to partial least squares discriminant analysis (OPLS-DA) were used for modeling. Multi-criteria assessment was used to identify the different metabolites between the two groups. Receiver operating characteristic (ROC) curve, pathway enrichment analysis and other methods were used to screen metabolites and pathways related to LM from lung adenocarcinoma.Results:There were no statistically significant differences in the proportions of age ( Z=-0.41, P=0.210) , gender ( χ2=1.19, P=0.275) , history of smoking ( χ2=2.86, P=0.091) , Karnofsky performance status score ( χ2=0.65, P=0.419) and increased intracranial pressure ( χ2=0.65, P=0.419) between the LM group and control group. The models of PCA (R2X was 0.608 and 0.583, Q2 was 0.462 and 0.513 in electrospray ion positive and negative modes, respectively) and OPLS-DA (R2Y was 0.967 and 0.889, Q2 was 0.959 and 0.852 in electrospray ion positive and negative modes, respectively) showed that the overall data quality was good. Meanwhile, the model interpretation rate and prediction rate were effective. The permutation tests duplicated for 200 times and showed no over-fitting of the established model. The metabolic profiles of the two groups were significantly different. A total of 30 endogenously differential metabolites were screened by using multi-criteria assessment. Six potential biomarkers with larger area under the curve (AUC) were identified through ROC curve analysis, including tyrosine (AUC=0.967, 95% CI: 0.906-1.000) , phenylalanine (AUC=0.992, 95% CI: 0.973-1.000) , pyruvate (AUC=0.976, 95% CI: 0.935-1.000) , tryptophan (AUC=0.935, 95% CI: 0.880-0.973) , glucose (AUC=0.932, 95% CI: 0.880-0.975) and adenosine monophosphate (AUC=0.993, 95% CI: 0.987-1.000) . The 30 selected differential metabolites were enriched and analyzed for metabolic pathways, and 20 relevant metabolic pathways were matched. Among them, the four metabolic pathways most likely to cause changes in metabolites were glycolysis and glucose metabolic synthesis, pyruvate metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion:Untargeted metabolomics analysis can effectively screen specific cerebrospinal fluid metabolites in lung adenocarcinoma patients with LM. Six potential metabolites such as tyrosine, phenylalanine, pyruvate, tryptophan, adenosine monophosphate, glucose and their metabolic pathways may be involved in the pathogenesis of LM from lung adenocarcinoma.

To summarize characteristics of the clinical manifestation，pathology and lower limb muscle magnetic resonance imaging in 11 patients diagnosed as myotonic dystrophy 1.Methods Eleven patients with myotonic myopathy 1，who were admitted to Nanjing Drum Tower Hopsital from January 2012 to October 2020，were chosen in our study. All patients accepted clinical examination，skeletal muscle biopsy，and 5 of them received lower limb muscle magnetic resonance imaging （MRI）. Clinical data were collected for retrospective analysis.Results All 11 patients were observed muscle myotonia，weakness or amyotrophy to some extent and the latter two symptoms were more serious in distal limb than in proximal. Under the light microscopy，type I filber atrophy in ten cases，nucleus moving inward，nucleus gathering and sarcoplasmic masses in some cases were found.That fatty infiltration appears asymmetrical distribution and more serious in distal limb compared with the proximal limb in five cases was observed by MRI. Among lower limbs，vastus medialis，vastus lateralis，vastus intermedius，tibialis anterior，gastrocnemius，soleus muscles were the most severely affected.Conclusion Muscle magnetic resonance imaging examination is a trustworthy method for definite diagnosis of myotonic myopathies.

BACKGROUND: Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM. METHODS: Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient. RESULTS: Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology. CONCLUSIONS The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application.

Chronic cough can occur in children of all ages, and the incidence rate and consultation rate increase each year.Clarifying the cause of chronic cough is the key to treatment.At present, there are no convenient, operable and unified standards for etiological analysis of chronic cough in the world.Therefore, the etiological analysis of chronic cough has always been a hot topic in clinical research.With the development of diagnosis and treatment technology, the role of pulmonary function and exhaled nitric oxide in the diagnosis of chronic cough has attracted attention.This article reviews the application value of pulmonary function combined with exhaled nitric oxide in etiology analysis of chronic cough in children, to provide reference for etiology analysis of chronic cough in children.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

Objective:To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT).Methods:Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed.Results:The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients.Conclusions:DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

Objective:To investigate and compare the therapeutic effect of Foley catheter balloon dilation and the traditional open reduction in the treatment of intussusception in children.Methods:A total of 68 children with intussusception treated by Foley catheter balloon dilatation by laparoscopic surgery or traditional open reduction in Department of Pediatric Surgery, the Second Hospital of Lanzhou University from August 2015 to July 2019 were retrospectively analyzed.Among them, there were 32 cases in the Foley catheter group and 36 cases in the traditional laparotomy group.Foley catheter group were treated with laparoscopic Foley catheter balloon dilatation, while the traditional open group were treated with traditional open surgery which was performed with finger dilatation.The results of surgical treatment, postoperative recovery, short-term complications, patient satisfaction and long-term complications were compared between the two groups.Results:Among the indexes of surgical treatment effect, the operation time[(0.4±1.1) h], intraoperative bleeding volume[(10.2±3.4) mL], incision size[(0.5±0.4) cm] and incidence of the rupture of intestine[6.3%(2/32 cases)] in the Foley catheter group were significantly lower than those in the traditional open group[(1.3±2.9) h, (40.5±2.1) mL, (5.1±0.7) cm, 30.6%(11/36 cases)], and the differences were statistically significant (all P< 0.05). Among the indexes of postoperative recovery and short-term complications, recovery time of gastrointestinal function[(1.2±3.1) d], length of hospital stay[(6.7±1.8) d], incidence of incision infection[9.4%(3/32 cases)]and incidence of incisional hernia(0) in the Foley catheter group were significantly lower than those in the traditional open group[(3.3±6.4) d, (7.3±0.9) d, 36.1%(13/36 cases), 16.7%(6/36 cases)], and the differences were statistically significant (all P<0.05). Among the indexes of family satisfaction and long-term complications, the score of family satisfaction in the Foley catheter group [(8.7±1.2) scores]was significantly higher than that in the traditional open group[(6.6±3.1) scores], and the incidence of adhesive intestinal obst-ructionin the Foley catheter group (0)was significantly lower than that in the traditional open group[0 vs.19.4%(7/36例)], and the differences were statistically significant(all P<0.05). Conclusions:Compared with traditional open reduction in the treatment of intussusception in children, Foley catheter balloon dilation has the advantages of short operation time, safe operation, low incidence of intestinal injury, less bleeding, and so on, and also has the advantages of small incision, fast recovery, short hospitalization time, high satisfaction of parents.In addition, the Foley catheter balloon dilation has a lower incidence of incisional infection, incisional hernia, postoperative intestinal adhesion and other complications.