Objective To construct the machine learning models based on the radiomic features of non-contrast and enhanced CT and to evaluate the predictive value in the risk stratification of gastrointestinal stromal tumor(GIST).Methods A total of 182 patients with pathologically confirmed GIST were randomly divided into a training set and a validation set at a ratio of 7∶3.The volume of interest(VOI)was outlined in the non-contrast phase,arterial phase and venous phase,and its radiomic features were extracted.The most valuable radiomic features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.The logistic regression(LR)classifier was used to construct the prediction models based on single-phase or multi-phase images.The predictive efficacy of the different models was compared by using receiver operating characteristic(ROC)curves.Results Four,three,and four radiomic features were selected in the non-contrast phase,arterial phase and venous phase,and 4 models were constructed in total.Among the single-phase models,the venous phase had better predictive efficacy,with the area under the curve(AUC)of 0.932[95％confidence interval(CI)0.873-0.969]and 0.924(95％CI 0.819-0.979)in the training and validation sets.The predictive efficacy of the combined model was improved,with the AUC of 0.946(95％CI 0.891-0.978)and 0.938(95％CI 0.838-0.986).Conclusion The venous phase model can predict the risk stratification of GIST accurately,and the prediction efficacy can be improved by combining the non-contrast and arterial phases.

Chinese medicine (CM) is an important resource for human life understanding and discovery of drugs. However, due to the unclear pharmacological mechanism caused by unclear target, research and international promotion of many active components have made little progress in the past decades of years. CM is mainly composed of multi-ingredients with multi-targets. The identification of targets of multiple active components and the weight analysis of multiple targets in a specific pathological environment, that is, the determination of the most important target is the main obstacle to the mechanism clarification and thus hinders its internationalization. In this review, the main approach to target identification and network pharmacology were summarized. And BIBm (Bayesian inference modeling), a powerful method for drug target identification and key pathway determination was introduced. We aim to provide a new scientific basis and ideas for the development and international promotion of new drugs based on CM.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Bayes Theorem ; Molecular Docking Simulation

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. METHODS: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. RESULTS: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01). CONCLUSIONS WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

Inflammatory bowel disease (IBD) is characterized by recurrent non ⁃ specific intestinal inflammatory responses. Intestinal fibrosis is an important cause of IBD complicated with intestinal obstruction. Nuclear factor erythroid 2⁃ related factor 2 (Nrf2) is a transcription factor that has anti ⁃ oxidative stress response in cells. In IBD, Nrf2 and its downstream regulated antioxidant enzymes achieve protective effects against intestinal fibrosis by inhibiting the activation of nuclear factor ⁃ κB, regulating T helper cell 17/regulatory T cell balance of intestinal immunity, and inhibiting transforming growth factor⁃β1/Smads signaling pathway. In this review, the structure of Nrf2, the specific mechanism of Nrf2's effect on intestinal fibrosis in IBD, and the recent studies on the treatment of IBD through Nrf2 pathway were reviewed in an attempt to provide a new direction for the prevention and treatment of IBD.

ObjectiveThis study aims to explore the potential molecular mechanism of Gegen Qinliantang （GQL） in the intervention of atherosclerosis （AS） based on network pharmacology and molecular docking. MethodThe active components and targets of each medicinal in GQL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and AS-related genes from 7 databases. Thereby， the anti-AS targets of GQL were screened out. Cytoscape 3.8.0 was employed to construct the "component-target" network， and STRING the protein-protein interaction （PPI） network. Core targets were screened out with CytoNCA. R clusterProfiler was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of target genes， which were then visualized. Finally， molecular docking of the top ten active components with the core targets of AS was performed and the binding affinity was compared with that between atorvastatin and the core targets. ResultIn the end， 150 active components of GQL， 20 289 AS targets， and 213 common targets were retrieved， and 48 core common targets were screened out. They were mainly involved in the GO terms of nuclear receptor activity， ligand activation， and transcription factor activity and the pathways of fluid shear force and AS， advanced glycation end products-receptor for advanced glycation end products （AGE/RAGE）， interleukin-17 （IL-17）， tumor necrosis factor （TNF）， Toll-like receptor pathways and other signaling pathways closely related to AS. The molecular docking results showed that the effective components of GQL had high binding affinity to core targets of AS， and the binding affinity was even higher than that between the atorvastatin and core targets. The five groups with high binding affinity were puerarin-TNF， baicalein-inducible nitric oxide synthase 2 （NOS2）， puerarin-NOS2， and formononetin-NOS2， wogonin-NOS2. ConclusionThe above result provides new ideas for further exploration of this classical decoction.

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Meridians ; Moxibustion

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Objective:To detect the levels of cytokines in peripheral blood of patients with chronic immune thrombocytopenia (ITP) and analyze their significance in the clinical prognosis of children with chronic ITP.Methods:Thirty patients with chronic ITP who were treated in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical Univercity from October 2015 to October 2018 were followed and enrolled in the experimental group and 40 healthy children in the same hospital were enrolled in the healthy control group.The levels of interleukin-2(IL-2), interferon-γ(IFN-γ), tumor necrosis factor(TNF), interleukin-4(IL-4), interleukin-6(IL-6), interleukin-10(IL-10) and interleukin-17A(IL-17A) in the experimental group and the healthy control group were detected by flow cytometry (CBA). The relationship between cytokines and prognosis of children with chronic ITP were analyzed.Results:Thirty patients with ITP were enrolled. The expressions of IL-2 and IL-17A in the experimental group before treatment were (7.86±3.90) ng/L and (10.45±12.35) ng/L, while those of IL-2 and IL-17A in the healthy control group were (3.11±2.41) ng/L and (2.97±7.04) ng/L. The levels of IL-2 and IL-17A in the experimental group were significantly higher than those in the healthy control group, and the differences were statistically significant ( t=-7.123, -5.582, all P<0.01). The expressions of IL-4 and IL-10 in the experimental group before treatment were (0.38±0.25) ng/L and (1.80±1.25) ng/L, while those of IL-4 and IL-10 in the healthy control group were (3.08±0.26) ng/L and (4.55±3.44) ng/L. The levels of IL-4 and IL-10 in the experimental group were significantly lower than those in the healthy control group, and the differences were statistically significant ( t=8.400, 5.653, all P<0.01). The expressions of IL-6, TNF and IFN-γ in the experimental group before treatment were (7.30±9.16) ng/L, (4.85±7.60) ng/L and (7.68±20.41) ng/L, while those of IL-6, TNF and IFN-γ in the healthy control group were (5.44±4.18) ng/L, (1.97±0.37) ng/L, (4.81±17.71) ng/L. There was no significant difference between the two groups ( P>0.05), and no significant difference in the levels of cytokines between the patients with chronic ITP before and 12 months after treatment ( P>0.05). Conclusions:The changes of T lymphocyte related cytokines are closely related to the pathogenesis and development of chronic ITP in children. There may be persistent immune dysfunction in children with chronic ITP. Dynamic monitoring of cytokines IL-2, IL-4, IL-10, IL-17A, especially IL-17A, is helpful to judge the prognosis of ITP in children, and may be of guiding significance in evaluating clinical prognosis.