ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology， molecular docking， and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards， Online Mendelian Inheritance in Man （OMIM）， PharmGKB， Therapeutic Target Database （TTD）， Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0， the STRING database was used to analyze the protein-protein interactions， and Cytoscape was used for the core target analysis and visualization. Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） were employed for enrichment analysis. Molecular docking was carried out in Autodock， and cell experiments were conducted to verify the prediction results. In the cell experiments， estradiol and progesterone （E₂+P） were used to intervene in human mammary epithelial/MCF-10A cells， and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 （CCK-8） was used to measure the cell proliferation， and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot， respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained， from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes， which may be related to protein kinase B （Akt）-related molecular functions， estrogen signaling pathway， prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 （ESR1）， serine/threonine kinase 1 （Akt1）， non-receptor tyrosine kinase （SRC）， and signal transducer and activator of transcription 3 （STAT3） all had strong binding activity with the nine active ingredients， suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway and the Janus kinase （JAK）/STAT3 signaling pathway. The results of cell experiments showed that E₂+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells （P<0.05）， while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E₂+P （P<0.05）. Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E₂+P （P<0.01）. The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K， Akt， JAK2， and STAT3 in MCF-10A cells treated with E₂+P （P<0.01）. The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K， p-Akt/Akt， p-JAK2/JAK2， and p-STAT3/STAT3 in MCF-10A cells treated with E₂+P （P<0.05）. ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells， which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.

Xihuang pills are a classic Chinese patent medicine following the theoretical principle of combining eliminating pathogen with reinforcing healthy qi in both local areas and the whole body， with the effects of clearing heat， detoxifying， alleviating edema， and dissipating mass. This medicine is traditionally used for treating carbuncle， furuncle， multiple abscess， carcinoma of breast， phlegm nodule， scrofula， lung abscess， and intestine abscess caused by fire depression， phlegm stasis， and heat toxin stagnation. It is used for treating malignant tumors， breast hyperplasia， herpes zoster， lymphadenitis， pelvic inflammatory disease， mastitis， vocal cord leukoplakia， and acne in modern medicine. Xihuang pills are now included in the 2020 edition of the Chinese Pharmacopoeia. The use of high-quality medicinal materials and modern technology enables full retaining of the active components in the medicinal materials. The chemical components in this medicine mainly include amino acids， terpenoids， fatty acids， fatty acid esters， phenols， bile acids， bile pigments， and volatile oils. Modern pharmacological studies have shown that a variety of active components such as bilirubin， bile acid， boswellic acid， and volatile oil in Xihuang pills interact with each other to exert anti-tumor， anti-breast hyperplasia， immunomodulatory， anti-inflammatory， and neuroendocrine-regulating effect. This paper reviews the research progress in the active components and pharmacological effects of Xihuang pills and predicts the quality markers （Q-markers） of this medicine according to the transmission， traceability， specificity， efficacy， measurability， and compound compatibility in the concept of Q-marker. It is suggested that bilirubin， bile acid， taurine， muskone， 11-carbonyl-β-boswellic acid， β-boswellic acid， 3-acetyl-11-keto-β-boswellic acid， octyl acetate， β-elemene， and myrrhone can be used as Q-markers of Xihuang pills， which can provide a basis for research on the material basis and the quality control of Xihuang pills.

Objective:To analyze the site of vestibular nerve damaged in patients with acute vestibular neuritis. Methods:Fifty-seven patients with acute vestibular neuritis were recruited, and each patient underwent caloric irrigation test, video head impulse test（vHIT） and vestibular evoked myogenic potentials（VEMPs）. The results were further analyzed. Results:Analysis of abnormal rates of different vestibular function tests: the abnormal rate of caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and posterior semicircular canal vHIT were 92.98%, 92.98%, 92.98%, and 52.63%, respectively. The abnormal rate of cervical vestibular evoked myogenic potentials（cVEMP） and ocular vestibular evoked myogenic potentials（oVEMP） were 52.63% and 89.47%. The abnormal rate of caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and oVEMP were significantly higher than posterior semicircular canal vHIT and cVEMP（P<0.01）. Combination analysis of different vestibular function tests: there are twenty-six patients（45.61%, superior and inferior vestibular nerve） with abnormal caloric irrigation test, video head impulse test, and VEMPs. There are twenty-five patients（43.86%, superior vestibular nerve） with abnormal caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and oVEMP. There are 4 patients（7.02%, inferior vestibular nerve） with abnormal posterior semicircular canal vHIT and cVEMP. There are two patients（3.51%, ampullary vestibular nerve） with abnormal caloric irrigation test, horizontal semicircular canal vHIT, and anterior semicircular canal vHIT. The rate of superior and inferior vestibular neuritis and superior vestibular neuritis were significantly higher than inferior vestibular neuritis and ampullary vestibular neuritis（P<0.01）. Conclusion:Acute vestibular neuritis subtypes can be divided into four categories: superior and inferior vestibular neuritis, superior vestibular neuritis, inferior vestibular neuritis, and ampullary vestibular neuritis. Video head impulse test can accurately assess the site of vestibular nerve damage in patients with acute vestibular neuritis. In addition, vHIT combined with VEMPs can provide objective evidence for the diagnosis of ampullary vestibular neuritis.
Humans ; Vestibular Neuronitis/diagnosis* ; Vestibule, Labyrinth ; Vestibular Nerve ; Semicircular Canals ; Head Impulse Test/methods*

Objective:To investigate the characteristics of videonystagmography (VNG) in multiple system atrophy (MSA) patients with vertigo as the main symptom.Methods:Twenty-eight MSA patients and 28 healthy volunteers were selected, and their basic clinical data, namely, gender, age of onset, course of disease, initial symptoms, and clinical manifestations, were collected. VNG was adopted to measure spontaneous nystagmus and carry out gaze test, saccade test, smooth tracking test, visual movement test, position test, and temperature test.Results:Among the MSA patients with vertigo as the main symptom, the number of MSA-C (the cerebellar type) cases ( n=22) was significantly higher than that of MSA-P (the parkinsonian type) cases ( n=6), and there was no statistically significant difference in gender, age of onset, and course of disease ( P>0.05). The incidence of gaze nystagmus was 45.5% (10/22) in the MSA-C group and 33.3% (2/6) in the MSA-P group, which were significantly higher than that in the control group ( P<0.05). The abnormal rate of saccade test was which were significantly higher than that in the control group ( P<0.05). The abnormal rate of saccade test was 36.4% (8/22) in the MSA-C group, and no abnormality was found in the MSA-P group and the control group. The rate of abnormal visual tracking was 77.3% (17/22) in the MSA-C group and 83.3% (5/6) in the MSA-P group, which were significantly higher than that of the control group ( P<0.05). The rate of decreased optokinetic nystagmus (OKN) or nystagmus asymmetry was 40.9% (9/22) in the MSA-C group and 83.3% (5/6) in the MSA-P group, which were significantly higher than that of the control group ( P<0.05). The abnormal rate of position test was 22.7% (5/22) in the MSA-C group and 33.3% (2/6) in the MSA-P group, which showed no statistically significant difference when compared with that of the control group ( P>0.05). In the temperature test, the abnormal rate of unilateral weakening was 22.7% (5/22) in the MSA-C group, which was significantly higher than those in the MSA-P group and the control group. The hyperresponsiveness rate of cold and heat stimulation was 4.5% (1/22) in the MSA-C group, while there was no hyperresponsiveness in both the MSA-P group and the control group. The failure rate of fixation inhibition was 63.6% (14/22) in the MSA-C group, and there was no failure in the control group. Conclusion:In MSA patients with vertigo as the main symptom, the incidence of abnormal eye movements, especially the symptoms of visual tracking abnormality, fixation inhibition failure, and gaze nystagmus, is relatively high. The results of this analysis can help clinical diagnoses.

Objective:To investigate the characteristics of videonystagmography (VNG) in multiple system atrophy (MSA) patients with vertigo as the main symptom.Methods:Twenty-eight MSA patients and 28 healthy volunteers were selected, and their basic clinical data, namely, gender, age of onset, course of disease, initial symptoms, and clinical manifestations, were collected. VNG was adopted to measure spontaneous nystagmus and carry out gaze test, saccade test, smooth tracking test, visual movement test, position test, and temperature test.Results:Among the MSA patients with vertigo as the main symptom, the number of MSA-C (the cerebellar type) cases ( n=22) was significantly higher than that of MSA-P (the parkinsonian type) cases ( n=6), and there was no statistically significant difference in gender, age of onset, and course of disease ( P>0.05). The incidence of gaze nystagmus was 45.5% (10/22) in the MSA-C group and 33.3% (2/6) in the MSA-P group, which were significantly higher than that in the control group ( P<0.05). The abnormal rate of saccade test was which were significantly higher than that in the control group ( P<0.05). The abnormal rate of saccade test was 36.4% (8/22) in the MSA-C group, and no abnormality was found in the MSA-P group and the control group. The rate of abnormal visual tracking was 77.3% (17/22) in the MSA-C group and 83.3% (5/6) in the MSA-P group, which were significantly higher than that of the control group ( P<0.05). The rate of decreased optokinetic nystagmus (OKN) or nystagmus asymmetry was 40.9% (9/22) in the MSA-C group and 83.3% (5/6) in the MSA-P group, which were significantly higher than that of the control group ( P<0.05). The abnormal rate of position test was 22.7% (5/22) in the MSA-C group and 33.3% (2/6) in the MSA-P group, which showed no statistically significant difference when compared with that of the control group ( P>0.05). In the temperature test, the abnormal rate of unilateral weakening was 22.7% (5/22) in the MSA-C group, which was significantly higher than those in the MSA-P group and the control group. The hyperresponsiveness rate of cold and heat stimulation was 4.5% (1/22) in the MSA-C group, while there was no hyperresponsiveness in both the MSA-P group and the control group. The failure rate of fixation inhibition was 63.6% (14/22) in the MSA-C group, and there was no failure in the control group. Conclusion:In MSA patients with vertigo as the main symptom, the incidence of abnormal eye movements, especially the symptoms of visual tracking abnormality, fixation inhibition failure, and gaze nystagmus, is relatively high. The results of this analysis can help clinical diagnoses.

To standardize diagnosis and treatment of vertigo,Chinese Society of Neurology and Editorial Board of Chinese Journal of Neurology organized vertigo experts to update 2010 expert consensus on diagnosis and treatment of vertigo.New version of multidisciplinary expert consensus on diagnosis and treatment of vertigo was published in November 2017 (hereinafter referred to as consensus).However,due to limitation on space,many details in consensus were not illustrated.Hence,the relevant contents will be stated in this article.

Objective To investigate the clinical efficacy of jejunal interposed single-tract and doubletract reconstruction after proximal gastrectomy for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction (AEG).Methods The prospective study was conducted.The clinicopathological data of 108 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to the Affiliated Tumor Hospital of Shanxi Medical University between August 2013 and November 2016 were collected.All the patients underwent proximal gastrectomy and were allocated into the 2 groups by random number table,including patients using single-tract jejunal interposition reconstruction in the single-tract group and patients using double-tract jejunal interposition reconstruction in the double-tract group.Digestive tract reconstruction:after end-to-side anastomosis between distal jejunum and esophagus and side-to-side anastomosis between posterior wall of the gastric remnant and jejunum,single-tract jejunal reconstruction was done through ligating jejunum at 3 cm below the anastomotic stoma,and then side-to-side anastomosis between proximal jejunum and jejunum was performed in the single-tract group.Patients in the double-tract group used the same digestive tract reconstruction,but jejunum was not ligated.The postoperative pathological examinations showed that patients with positive lymph nodes or tumor invading all layers of gastric wall underwent chemotherapy.Observation indicators:(1) intra-and post-operative situations;(2) follow-up situations.Follow-up using telephone interview was performed to detect postoperative complication,gastrointestinal function and body mass index (BMI) up to November 2017.Measurement data with normal distribution were represented as-x± s and comparison between groups was analyzed using t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was analyzed using the nonparametric test.Repeated measurement data were analyzed by the repeated measures ANOVA.Comparisons of count data were done using chi-square test.Ordinal data were analyzed by the Kruskal Wallis H test.Results One hundred and eight patients were screened for eligibility,including 55 in the single-tract group and 53 in the double-tract group.(1) Intra-and post-operative situations:total operation time,digestive tract reconstruction time,volume of intraoperative blood loss,time to initial anal exsufflation,postoperative complications,cases with gastroesophageal reflux,intestinal obstruction and Visick grading ＞ Ⅱ and duration of postoperative hospital stay were respectively (145±26) minutes,(30±6) minutes,(181±37) mL,(53± 16) hours,1,1,1,(10.0±2.4) days in the singletract group and (139±29)minutes,(26±3)minutes,(176±31)mL,(50±17) hours,3,0,3,(9.4±l.4)days in the double-tract group,with no statistically significant difference between groups (t =0.725,0.219,0.162,-0.576,x2 =2.960,5.830,t =-0.993,P＞0.05).Four patients with gastroesophageal reflux received motilium and omeprazole therapy for 2 weeks,and were improved by symptomatic treatment such as increasing the solid food intake.One patient in the single-tract group had internal hernia-induced intestinal obstruction and was cured by reoperation.There was no anastomotic leakage,bleeding,infection,dumping syndrome and gallstone between groups.Of 108 patients,71 underwent 6-cycle SOX chemotherapy,including 67 with perigastric lymph node metastasis and 4 with tumor invading all layers of gastric wall.(2) Follow-up situations:108 patients were followed up for 12.0-48.0 months,with a median time of 28.6 months.During the follow-up,bowel sound in the double-tract group and single-tract group was 8 times / minute (range,5-12 times / minute) and 3 times /minute (range,2-5 times/ minute),with a statistically significant difference between groups (Z=-0.692,P＜0.05).The single food intake,serum gastrin level,ratio of serum pepsinogen Ⅰ and Ⅱ levels and BMI from preoperation to postoperative 12 months were from (1 117± 129)mL to (817± 127)mL,from (12±5)pmol/L to (41±13) pmol/L,from 11.3±2.8 to 5.1±2.2,(65±7)kg to (63±5) kg in the single-tract group and from (1 095±118)mL to (783±80)mL,from (10±4)pmol/L to (40±10)pmol/L,from 12.4±2.9 to 4.2±1.3,from (63±6) kg to (58±6)kg in the double-tract group,respectively,with no statistically significant difference in single food intake,serum gastrin level and ratio of serum pepsinogen Ⅰ and Ⅱ levels between groups (F =0.468,0.108,0.161,P＞0.05).There was a statistically significant difference in changing trend of BMI between groups (F=24.930,P＜0.05).Conclusion Jejunal interposed single-tract and double-tract reconstruction after proximal gastrectomy for Siewert type Ⅱ and Ⅲ AEG have the same surgical safety and don't affect secretion function of gastric remnant,but there are frequent bowel sounds and obvious weight loss.

Objective To observe the biochemical indicators and lifestyles of patients with non-alcoholic fatty liver disease (NAFLD),and analyse the risk factors of induced NAFLD.Methods A total of 258 in-and out-patients of NAFLD were included in the present study,the control group consisted of 213 examinationers with nonfatty liver disease.All samples were being blood biochemical indicator detection and lifestyle survey.Results Some blood biochemical index of NAFLD patients such as TC(5.48 ± 1.10) mmol/L,TG(2.31 ± 1.25) mmol/L,ALT (51.35 ± 26.18) U/L,AST (42.37 ± 28.32) U/L,FPG (5.62 ± 3.24) mmol/L,GGT (58.47 ± 43.25) U/L and UA (398.51 ± 96.85) μmol/L were higher than those of the control group (t =3.423,5.250,7.402,4.348,3.326,6.683,3.891,all P ＜ 0.01) ; and the incidence of hyperlipidemia,hypertension (21.71％),diabetes (22.09％),BMI(26.85 ± 3.45) or metabolic syndrome (44.57％) etc.Those indexes in NAFLD patients were significantly higher than those in the control group (x2 =8.14,10.55,58.48,t =10.73,all P ＜ 0.01).By multivariable Logistic regression analysis,TG,WI,BMI,HOMA-IR,lack of exercise,high-fat diet were independent risk factors for NAFLD (all P ＜ 0.05).Conclusion Patients with NAFLD is closely correlated to metabolic abnormalities,reasonable diet and a healthy lifestyle is an effective way of prevention and treatment of this disease.

Objective To compare the prevalence of patent foramen ovale (PFO) in young and middle-aged patients with cryptogenic ischemic stroke (CS) and in normal population.Methods The casecontrol study included consecutive 318 young and middle-aged patients with CS and 336 normal control subjects with matched age and sex for group comparisons.Stroke risk factors including hypertension,diabetes mellitus,hyperlipidemia,ischemic heart disease,atrial fibrillation,carotid atherosclerosis plagues and smoking,etc.were studied.Transesophageal echocardiography (TEE) were performed to detect the presence of PFO.The prevalence of PFO and difference of risk factor levels between the groups was compared.Then the odds ratios (OR) of a PFO was estimated in CS patients versus control subjects.Results The prevalence of PFO was significant higher in patients with CS than in control subjects (145/318,45.6 ％ versus 46/336,13.7％,P ＜0.001).The odds ratio(OR) for PFO in CS for patients versus control subjects was 5.3 (confidence interval,3.6 to 7.8).The mean size of PFO was larger in stroke group than that in control group (P ＜ 0.001).There were no significant differences in levels of other stroke risk factors between two groups.Conclusions PFO may play an important role in etiology of CS in young and middleaged adults.Larger and longer PFOs may be more concomitant with ischemic attacks.More efforts should be employed in patients with CS to detect PFO for further treatment.

Objective To explore the value of the diagnosis of middle cerebral artery (MCA) stenosis with transcranial Doppler ultrasound (TCD). Methods The clinical data in patients with ischemic cerebrovascular disease examined with digital subtract angiography (DSA)and TCD were analyzed retrospectively. DSA was used as a gold standard to analyze the sensitivity and specificity of the diagnosis of MCA stenosis with TCD. The normal and TCD blood flow velocity with different degrees of stenosis were compared. The best cut-off point of the TCD blood flow velocity of MCA at different degree of stenosis was calculated. Results DSA confirmed that 103 patients had MCA stenosis or occlusion, in which 12 were mild stenosis, 22 were moderate stenosis, 40 were severe stenosis, and 39 were occlusion. Compared to DSA, the sensitivity of TCD in detection of moderate and severe MCA stenosis or occlusion was 78. 8%, the specificity was 96. 0%, and the accuracy was 93. 0%, the missed diagnosis rate was 21. 2%, and the misdiagnosis rate was 4. 0%. As to the blood flow velocity, there was no significant difference between the mild stenosis and normal groups; while there was significant difference between the moderate stenosis and normal groups (P ＜0. 001). In addition, there was no significant difference in blood flow velocity between the moderate stenosis and severe stenosis groups. Determining the cut-off value of the best peak systolic velocity of the moderate stenosis was 163. 5 cm/s, while the best cut-off value of the mean velocity was 108. 5 cm/s. Conclusions TCD has certain advantages in the diagnosis of the MCA stenosis or occlusion, and it can be used as a safe and inexpensive screening means before DSA examination.