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Objective:To investigate the expression of retinoic acid receptor responsive gene 2 (RARRES2), microtubule microfilament cross-linking factor 1 (MACF1), and core protein polysaccharide (DCN) in cerebrospinal fluid (CSF) of patients with neurosyphilis, and their diagnostic value for neurosyphilis.Methods:A total of 64 non neurosyphilis syphilis patients (syphilis group) and 78 neurosyphilis patients (neurosyphilis group) admitted to the Second Hospital of Nanjing between June 2020 and September 2022 were included. Among neurosyphilis patients, there were 48 early neurosyphilis patients (early group) and 30 late neurosyphilis patients (late group). Patients with neurosyphilis are treated with routine symptomatic therapy and antibiotic therapy to expel syphilis. The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis before and after treatment were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients with neurosyphilis before and after treatment. The diagnostic value of various indicators for neurosyphilis was analyzed using receiver operating characteristic (ROC) curves.Results:The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis were higher than those in the syphilis group (all P<0.001). The mRNA levels of RARRES2, MACF1, and DCN in the CSF of patients with advanced neurosyphilis were higher than those in the early group (all P<0.001). Compared with before treatment, the NIHSS score and RARRES2, MACF1, and DCN mRNA levels of neurosyphilis patients decreased after treatment (all P<0.001). The area under the curve (AUC), sensitivity, and specificity of the combined diagnosis of RARRES2, MACF1, and DCN mRNA in CSF for neurosyphilis were 0.995%, 100.00%, and 93.75%, respectively. The AUC and sensitivity were higher than those of individual diagnosis. Conclusions:The expression of RARRES2, MACF1, and DCN is elevated in CSF of patients with neurosyphilis, and is associated with disease severity and treatment response. These three genes may be candidate biomarkers for diagnosing neurosyphilis.
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Background:Gastroesophageal reflux disease(GERD)is a common digestive system disease with typical symptoms of acid reflux and heartburn,and high sensitivity of esophagus is an important cause of heartburn and other symptoms.TRPV1 and NaV1.8 may play an important role in the regulation of esophageal hypersensitivity,and the specific mechanism is not yet clear.Aims:To detect the expression levels of TRPV1 and NaV1.8 in esophageal sensory neuron in GERD state and explore their role in mediating esophageal hypersensitivity.Methods:Twelve guinea pigs were randomly divided into control group and GERD group.The GERD guinea pig model was established by drinking hydrochloric-pepsinogen acid water,the body mass of guinea pigs was monitored,the esophageal inflammatory histological score was performed,and the successful construction of the GERD model was verified by measuring the expression indicators of inflammatory factors.The heart rate variability method was used to detect whether the guinea pigs were in the state of visceral hypersensitivity.The expression and co-expression of TRPV1 and NaV1.8 in esophagus,nodular ganglion and jugular ganglion were detected by immunofluorescence,Western blot and real-time fluorescence quantification.Results:Compared with the control group,the score of esophageal inflammatory histology in GERD group was much higher than that in the control group(0.96 vs.0.22).The contents of esophageal inflammatory factors interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α were significantly increased(P<0.05),while the contents of anti-inflammatory factor IL-10 were decreased(P<0.05).The index of heart rate variability,low frequency to high frequency ratio(LF/HF)had no significant difference between the GERD group and the control group(P>0.05),and the LF/HF in the GERD group was higher than that in the control group after the molding(P<0.05).In esophagus and jugular,the expression levels of TRPV1 and NaV1.8 in GERD group were increased and the co-expression levels were up-regulated(P<0.05),while the expression levels in nodose were not significantly changed(P>0.05).Conclusions:In the case of esophageal acid exposure,the expression levels of TRPV1 and NaV1.8 in the esophageal mucosal epithelium increased,while the expression levels in jugular ganglion were up-regulated,thus promoting the transmission of pain signals in the vagus nerve pathway,and ultimately leading to the occurrence of esophageal hypersensitivity.
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Background: Studies have shown that transient receptor potential (TRP) channels play important roles in gastroesophageal reflux disease (GERD), however, the relationship between TRPV1 and TRPM8 in reflux esophagitis (RE) remains unclear. Aims: To investigate the expressions of TRPV1, TRPM8 and their correlation in guinea pigs with RE. Methods: Thirty male guinea pigs aged 3⁃4 weeks were randomly divided into 3 groups: blank control group, negative control group and model group, with 10 animals in each group. Guinea pigs in model group and negative control group were given esophageal perfusion with 0.1 mol/L HCl containing 0.5% pepsin and normal saline, respectively, once a day for 14 days; guinea pigs in blank control group were free to drink sterile water for 14 days. On day 15, the esophagus was dissected for macroscopic and histopathological examination, and Western blotting and/or real⁃time PCR were used to detect the expression levels of TRPV1, TRPM8, GNAQ (an isoform of G protein), and the tight junction proteins and proinflammatory cytokines in esophageal tissue. The co⁃localization of TRPV1 and TRPM8 was assessed by immunofluorescence. Results: Esophageal mucosal congestion, hyperplasia of esophageal epithelial cells, infiltration of inflammatory cells, as well as up⁃regulation of proinflammatory cytokines and down⁃regulation of tight junction proteins were observed in esophageal tissue of guinea pigs in model group, which indicated the successful RE model construction. As compared with the negative control group, expression levels of TRPV1 and GNAQ mRNA and protein were significantly increased, while expression levels of TRPM8 mRNA and protein were significantly reduced in esophageal tissue of guinea pigs in model group (all P<0.05). TRPV1 and TRPM8 channels were co ⁃ localized in the lamina propria of esophageal mucosa. Conclusions: There is a certain equilibrium mechanism between TRPV1 and TRPM8 channels in RE models. G protein⁃coupled receptor signaling pathway and the downstream TRPV1/TRPM8 might be involved in the occurrence and development of GERD.
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Gastroesophageal reflux disease (GERD) is a common digestive disease characterized by heartburn and acid reflux. In recent years, many studies have shown that esophageal hypersensitivity is an important pathophysiological mechanism involved in the occurrence and development of heartburn. Esophageal sensory receptors including transient receptor potential vanilloid 1 (TRPV1), prostaglandin E
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Objective:To study the clinical, endoscopic and histological characteristics of heterotopic gastric mucosa in upper esophagus (HGMUE).Methods:A Total of 177 patients who underwent gastroscopy and were diagnosed as having HGMUE at the Endoscopy Center of Wuhan Union Hospital from January 2017 to December 2017 were included in the study. According to the gastroesophageal reflux disease symptom questionnaire (GERD-Q) scores, patients were divided into the HGMUE group (GERD-Q<8, n=101) and GERD+HGMUE group (GERD-Q≥8, n=76). The data of clinical, endoscopic and histological characteristics were analyzed. Results:Among the 177 HGMUE cases, there were 111 males (62.71%) and 66 females (37.29%), 76 (42.94%) with GERD, and 101 (57.06%) without GERD. The most common symptom was continuous clearing throat [54.24% (96/177)], followed by foreign body sensations of throat [48.59% (86/177)], and gastroesophageal reflux symptoms such as heartburn, chest pain, indigestion, acid reflux [48.59% (86/177)]. In the HGMUE group, the occurrence rate of clearing throat was the highest [42.57% (43/101)], then foreign body sensations of throat accounted for 33.66% (34/101), and gastroesophageal reflux symptoms was 27.72% (28/101). In the HGUME+GERD group, the most common symptom was gastroesophageal reflux symptoms [76.32% (58/76)], then clearing throat [69.74% (53/76)] and foreign body sensations of throat [68.42% (52/76)]. Under gastroscopy, 177 heterotopic gastric lesions were found under gastroscopy with orange-red round, oval or elongated island like ones, most of which were flat and a few slightly protruded from the peripheral plane. There were 132 (74.58%) single-lesion cases, 38 (21.47%) 2-lesion, and 7 (3.95%) 3- or more-lesion cases; there were 37 (20.90%) small lesions (maximum diameter <0.5 cm), and 74 (41.81%) median-size lesions (maximum diameter of 0.5-1.0 cm), and 66 (37.3%) larger lesions (maximum diameter >1.0 cm). Among the 30 [16.95% (30/177)] samples of mucosal tissue, 15 [50.00% (15/30)] were mainly cardia gland, 8 [26.67% (8/30)] were mainly pyloric gland, 6 [20.00% (6/30)] were mixed type, and 1 [3.33% (1/30)] was squamous epithelium. In the immunohistochemical test, 20 cases [66.67% (20/30)] showed positive of H +/K +-ATPase, and 10 cases [33.33% (10/30)] were negative. Conclusion:HGMUE is more common in male patients, and may be combined with GERD. Among them, patients with combined GERD are more likely to develop laryngopharyngeal reflux. The heterotopic gastric mucosas lesions are orange-red round, oval or elongated island-like under gastroscopy, and most of them are flat, single and median- or large-sized. Histological types are mostly fundic glands, and H +/K +-ATPase positive is more common. It is speculated that acid secretion may be an important factor leading to throat symptoms.
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Objective To investigate the effect of subclinical epileptiform discharges (SED) on the cognition of adult patients with epilepsy,exploring the mechanism of SED that leads to cognitive impairment in adult patients with epilepsy to raise physicians' attention about SED.Methods Patients were collected in the Department of Neurology,China-Japan Union Hospital of Jilin University from March 2016 to March 2017.Sixty adult patients with epilepsy without clinical episodes in the last three months were selected as SED group and 40 healthy volunteers as control group.Medical history of the SED group was recorded in detail.All patients were examined by Self-rating Anxiety Scale,Self-rating Depression Scale,Pittsburgh Sleep Quality Index scale in order to exclude organic brain disorders,metabolic diseases,anxiety,depression,sleep disorders and drug-induced cognitive dysfunction.Subjects in the two groups received Montreal Cognitive Assessment (MoCA),electroencephalogram and blood oxygen level dependent functional magnetic resonance imaging examination.Finally,the results were compared between the two groups.Results ①SED had different effects on cognitive function in adult patients with epilepsy,and the MoCA score (26(22,27)) showed statistically significant difference compared with the control group (29 (28,29),Z =-6.26,P =0.00).②Different discharges indexes showed different effects on cognitive function aspects.Cognitive impairment was significant when the discharges indexes were > 10% (discharges indexes 1%-10%:MoCA score 26(26,28),discharges indexes 10%-50%:MoCA score 22(19.5,25),Z =-4.74,P =0.00).③The cognitive function of epilepsy patients was positively correlated with the duration of education (r =0.41,P =0.00) and the time interval to recent seizure (r =0.31,P =0.02),and negatively correlated with SED (r =-0.57,P=0.17).There was no correlation between cognitive function and duration of disease and onset age.The SED was the main influencing factor of cognitive function in epilepsy.④Compared with healthy people,epilepsy patients with SED showed differences in resting brain function network connection,with strong connective regions at the right inferior temporal gyrus,right hippocampus,bilateral thalamus,with weak connective regions at the double medial upper frontal gyrus,lateral dorsal frontal gyurs.Conclusions SED had an effect on the cognitive function of adult patients with epilepsy.The mechanism of cognitive impairment in adult epilepsy with SED may be related to abnormal brain function in cognitive-related areas.
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Objective To analyze the endoscopic features of patients with the lower esophageal sphincter (LES) and crural diaphragm (CD) separation and explore its significance in hiatus hernia (HH) diagnosis.Methods From January 2011 to June 2012,the data of patients underwent esophagus high resolution manometry (HRM) examination were retrospectively analyzed and of which the patients with LES-CD separation were selected.Patients who received digestive tracts operation or lack of complete endoscopic date were excluded.A total of 93 cases were enrolled for analysis.According to Chicago Criteria,the cases were divided into three groups.There were 21 cases in type Ⅰ group (LES-CD separation<1 cm),37 cases in type Ⅱ group (LES-CD separation≥l cm and <2 cm),35 cases in type Ⅲ group (LES-CD separation≥2 cm).The differences among groups in endoscopic features were analyzed.HRM were taken as golden standard,the sensitivity and specificity of endoscopy in HH diagnosis were analyzed.Measurement data were expressed as x ± s,one-way ANOVA was performed for multi-groups comparisons,LSD method or Dunnett T3 test for pairwise comparisons and chi-square test or Fisher's exact test for two groups' comparisons.Results There were no significant differences in the distance between esophagus gastric junction (EGJ) and foreteeth of the three groups (P>0.05).Distances between EGJ and diaphragmatic HH pressure impression in type Ⅲ group,type Ⅱ group and type Ⅰ group were (3.57±0.78) cm,(1.89±0.81) cm and (1.14±0.67) cm,respectively and the differences were significant (LSDt=9.26,11.44,3.57; all P<0.05).The percentage of continuously-open cardia and showing pressure impression of the gastric pouch of type Ⅲ group was higher than that of type Ⅱ group and the percentage of continuously-open cardia and showing pressure impression of gastric poach of type Ⅱ group was higher than that of type Ⅰ group (80.0%,40.5% and 4.8%,x2 =11.64,29.76 and 8.59; 91.4%,27.0% and 4.8%,x2 =30.69,40.73 and 4.32' all P<0.05).The occurrence rates of the His angle blunting and sac of type Ⅲ group were higher than those of typeⅡ group and type Ⅰ group (74.3% and 77.1%,24.3% and 24.3%,4.8% and 4.8%,x2 =17.97 and 25.41,both P<0.05),there was no significant difference between type Ⅱ group and type Ⅰ group (P>0.05).The rates of esophagitis of type Ⅲ group and type Ⅱ group were higher than that of type Ⅰ group (71.4%,59.5% and 14.3%,x2 =17.14 and 11.15,both P<0.05),there was no significant difference between type Ⅲ group and type Ⅱ group (P>0.05).There was one case of Barrett's esophagus in each group.The sensitivity and specificity of endoscopy in HH diagnosis were 91.4% and 81.0%,respectively.Conclusions The distance between EGJ and hiatal pressure impression,continuously-open cardia,the His angle blunting,hiatal pressure impression of the gastric pouch and hernia sac were important indicators of HH endoscopic features.The sensitivity of endosocopy is higher than the spcificity of endosocopy in HH diagnosis.
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This study investigated whether the curative effect of short-pulse gastric electrical stimulation (GES) on the vasopressin-induced dyspeptic symptoms was mediated by central opioid peptide-producing neurons. Five female beagle dogs implanted with 1 pair of electrodes in gastric serosa were used in a two-experiment study. In experiment one, the brain was scanned by positron emission tomography in 3 dogs with and without short-pulse GES, and the radioactivity in nuclei of solitary tract (NST) and hypothalamus was detected. Experiment two was composed of 4 sessions. In session one, the dogs were injected with vasopressin in the absence of short-pulse GES. With session two, the short-pulse GES was simultaneously given via the electrodes with the injection of vasopressin. In sessions three and four, naloxone and naloxone methiodide was administered respectively in the presence of short-pulse GES. Motion sickness-like symptoms were scored and compared among the different sessions. The results showed that the short-pulse GES significantly increased the radioactivity in NST and hypothalamic nuclei (P<0.05, vs control). The short-pulse GES could ameliorate the vasopressin-induced motion sickness-like symptoms in dogs. Naloxone, but not naloxone methiodide could attenuate the curative effects of short-pulse GES. It is concluded that NST and hypothalamic nuclei may participate in the mediation of the curative effects of short-pulse GES on dyspepsia-like symptoms. Central opioid peptide-containing neurons presumably mediate the therapeutic effect on dyspeptic symptoms of short-pulse GES.
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Objective To explore the effects of exogenous methionine on arsenical distribution in liver,blood and brain of mice exposed to sodium arsenite through drinking water. Methods The female Kunming mice were randomly divided into control group, the alone arsenic exposure group , the low level methionine intervention group, the moderate level methionine intervention group and the high level methionine intervention group, eight mice in each group . The mice in the experimental groups were exposed to sodium arsenite through drinking water at 50 mg/L arsenic for four consecutive weeks. And at the fourth week the 5 groups were treated intraperitoneally with saline solution (control and As group),100 mg/kg b.w,200 mg/kg b.w or 400 mg/kg b.w methionine,respectively . Twenty-four hours after cessation of methionine administration,mice were anaesthetized and rapidly dissected. The samples of blood,liver and brain were removed immediately for arsenic species analysis. Levels of inorganic arsenic (iAs),monomethylarsonic acid (MMA) and dimethylarsenic acid (DMA) were determined by HG-AAS method. Then total arsenic speciation( TAs), primary methylation ratio( PMR)and secondary methylation ratio( SMR)in each tissue were calculated. Results Compared with the control group, the levels of iAs, MMA, DMA and TAs in liver, brain and blood, were significantly higher in all experimental groups ( P