Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Motor imaging therapy is of great significance to the rehabilitation of patients with stroke or motor dysfunction, but there are few studies on lower limb motor imagination. When electrical stimulation is applied to the posterior tibial nerve of the ankle, the steady-state somatosensory evoked potentials (SSSEP) can be induced at the electrical stimulation frequency. In order to better realize the classification of lower extremity motor imagination, improve the classification effect, and enrich the instruction set of lower extremity motor imagination, this paper designs two experimental paradigms: Motor imaging (MI) paradigm and Hybrid paradigm. The Hybrid paradigm contains electrical stimulation assistance. Ten healthy college students were recruited to complete the unilateral movement imagination task of left and right foot in two paradigms. Through time-frequency analysis and classification accuracy analysis, it is found that compared with MI paradigm, Hybrid paradigm could get obvious SSSEP and ERD features. The average classification accuracy of subjects in the Hybrid paradigm was 78.61%, which was obviously higher than the MI paradigm. It proves that electrical stimulation has a positive role in promoting the classification training of lower limb motor imagination.
Brain-Computer Interfaces ; Electric Stimulation ; Electroencephalography ; Humans ; Imagination ; Lower Extremity ; Movement

Objective:To understand the epidemiological characteristics and clinical features of rotavirus-, norovirus-, adenovirus-and astrovirus-associ ated acute gastroenteritis in children under 5 years old in Beijing from Octorber, 2015 to March, 2017.Methods:In the intestinal clinic of 6 hospitals in 6 districts of Beijing, information and stool samples of the first 30 patients with acute gastroenteritis who are under the age of 5 years are collected monthly.Rotavirus, norovirus, adenovirus and astrovirus are identified by PCR.Descriptive epidemiological method was used to describe the epidemiological characteristics of diarrhea caused by rotavirus, norovirus, adenovirus and astrovirus in Beijing. One-way analysis of variance was used to analyze the Vesikari clinical severity score of of acute gastroenteritis caused by each virus. Unconditional logistic regression analysis was used to analysis the associated factors of clinical features.Results:Of the 2 052 samples, 709 (34.6%) were non-mixed infections: the positive rate of rotavirus, norovirus, adenovirus and astrovirus were 20.0%, 7.5%, 4.2% and 2.9%, respectively. A total of 135 cases (6.6%) were mixed infection. The mean and standard deviation of Vesikari clinical severity score was 8.0±3.1 for rotavirus associated acute gastroenteritis, which was significantly higher than norovirus (6.4±2.4, P<0.001), adenovirus (6.2±2.1, P<0.001) and astrovirus (6.1±2.0, P<0.001). The comparison of clinical features showed that compared with astrovirus, the children under 5 years old infected with rotavirus were more likely to have a diarrhea ≥5 days ( OR=3.334), have vomiting ≥3 times within one day ( OR=8.788), have vomiting≥1 day ( OR=3.963), have a Vesikari clinical severity score ≥11 severe cases ( OR=13.194). Norovirus infected cases were prone to have vomiting≥3 times in 1 day ( OR=5.710).Adenovirus infected cases were prone to have a diarrhea≥5 days ( OR=2.616). When using rotavirus as a reference, children under 5 years of age were less likely to develop fever≥38.4 ℃ after infection with norovirus ( OR=0.397) or adenovirus ( OR=0.280). Conclusions:The results of this study showed that the characteristics of acute gastroenteritis caused by different viruses are different. The clinical symptoms caused by rotavirus are more serious. Children under 24 months of age are at high risk of rotavirus infection. Effective preventive measures such as vaccination should be taken as soon as possible.

Objective:To understand the epidemiological characteristics and clinical features of rotavirus-, norovirus-, adenovirus-and astrovirus-associ ated acute gastroenteritis in children under 5 years old in Beijing from Octorber, 2015 to March, 2017.Methods:In the intestinal clinic of 6 hospitals in 6 districts of Beijing, information and stool samples of the first 30 patients with acute gastroenteritis who are under the age of 5 years are collected monthly.Rotavirus, norovirus, adenovirus and astrovirus are identified by PCR.Descriptive epidemiological method was used to describe the epidemiological characteristics of diarrhea caused by rotavirus, norovirus, adenovirus and astrovirus in Beijing. One-way analysis of variance was used to analyze the Vesikari clinical severity score of of acute gastroenteritis caused by each virus. Unconditional logistic regression analysis was used to analysis the associated factors of clinical features.Results:Of the 2 052 samples, 709 (34.6%) were non-mixed infections: the positive rate of rotavirus, norovirus, adenovirus and astrovirus were 20.0%, 7.5%, 4.2% and 2.9%, respectively. A total of 135 cases (6.6%) were mixed infection. The mean and standard deviation of Vesikari clinical severity score was 8.0±3.1 for rotavirus associated acute gastroenteritis, which was significantly higher than norovirus (6.4±2.4, P<0.001), adenovirus (6.2±2.1, P<0.001) and astrovirus (6.1±2.0, P<0.001). The comparison of clinical features showed that compared with astrovirus, the children under 5 years old infected with rotavirus were more likely to have a diarrhea ≥5 days ( OR=3.334), have vomiting ≥3 times within one day ( OR=8.788), have vomiting≥1 day ( OR=3.963), have a Vesikari clinical severity score ≥11 severe cases ( OR=13.194). Norovirus infected cases were prone to have vomiting≥3 times in 1 day ( OR=5.710).Adenovirus infected cases were prone to have a diarrhea≥5 days ( OR=2.616). When using rotavirus as a reference, children under 5 years of age were less likely to develop fever≥38.4 ℃ after infection with norovirus ( OR=0.397) or adenovirus ( OR=0.280). Conclusions:The results of this study showed that the characteristics of acute gastroenteritis caused by different viruses are different. The clinical symptoms caused by rotavirus are more serious. Children under 24 months of age are at high risk of rotavirus infection. Effective preventive measures such as vaccination should be taken as soon as possible.

Objective To observe the effects of fecal microbiota transplantation on intestinal microbiota and brain function in sepsis rats. Methods Sixty male Sprague Dawley (SD) rats were divided into sham operation group, model group and fecal microbiota transplantation (FMT) group by random number table, each group 20 rats. The rat model of sepsis was established by injection of lipopolysaccharide (LPS) 10 mg/kg in tail vein. FMT group received nasogastric infusion of feces from healthy donor. Fecal samples were collected on the 6th day after the modeling to detect the levels of intestinal microbiota composition; the brain function was also evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats in different groups, the brain tissues were taken, the levels of protein expression and positive cells of Iba-1 in brain tissue were detected by Western Blot and immunohistochemistry method. Results ① Intestinal flora analysis showed that: the diversity index and Chaol index of the intestinal microbiota in model group were significantly lower than that in sham operation group (observed species:282±40 vs. 473±37, Chao1 index: 730±21 vs. 837±27, both P < 0.05); compared with the model group, the diversity index and Chaol index in FMT group were obviously higher (observed species: 461±20 vs. 282±40, Chao1 index:840±16 vs. 730±21, both P < 0.05). At phylum, family, genus level analysis showed that the proportion of Firmicutes phylum and Fusobacterium were obviously lower than those of sham operation group [Firmicutes phylum (22.12±1.34)% vs. (78.01±1.23)%, Fusobacterium: (2.03±0.17)% vs. (5.03±0.19)%, both P < 0.05], and the proportions of Proteobacteria, Bacteroidetes phyla and Acidaminococcaceae, Fusobacteriaceae, Enterbacteriacecae, Alistipes were markedly higher in model group [Proteobacteria: (70.21±2.35)% vs. (19.45±2.17)%, Bacteroidetes phyla: (4.12±0.19)% vs. (2.50±0.64)%, Acidaminococcaceae: (12.51±0.87)% vs. (1.01±0.12)%, Fusobacteriaceae: (13.62±1.27)% vs. (2.31±0.19)%, Enterbacteriacecae: (18.24±2.13)% vs. (4.15±1.51)%, Alistipes: (4.53±0.27)% vs. (1.47±0.33)%, all P < 0.05]; compared with the model group, the proportion of Firmicutes phylum and Faecalibacterium in FMT group were significantly higher [Firmicutes phylum: (72.14±2.31)% vs. (22.12±1.34)%, Faecalibacterium: (5.01±0.27)% vs. (2.03±0.17)%, both P < 0.05], and Proteobacteria, Bacteroidetes phyla and Acidaminococcaceae, Fusobacteriaceae, Enterbacteriacecae in FMT group were obviously lower [Proteobacteria: (14.23±1.98)% vs. (70.21±2.35)%, Bacteroidetes phyla: (3.15±0.18)% vs. (4.12±0.19)%, Acidaminococcaceae: (0.91±0.11)% vs. (12.51±0.87)%, Fusobacteriaceae: (1.25±0.15)% vs. (13.62±1.27)%, Enterbacteriacecae: (3.50±0.21)% vs. (18.24±2.13)%, all P < 0.05]. ② EEG analysis showed that the percentages of δ wave in EEG in model group was significantly higher after modeling than that in sham operation group [(16.86±0.50)% vs. (10.67±0.65)%, P < 0.05]; the ratios of δ wave in EEG was significantly lower in FMT group than that in the model group [(12.87±0.60)% vs. (17.35±0.41)%, P <0.05]. The incidence of abnormal EEG in sham operation group was 0, the incidence of abnormal EEG in model group was significantly increased [the ratios of δpredominant wave, θpredominant wave, low-voltage were 66.7% (6/9), 66.7% (6/9), 77.8% (7/9) respectively], the ratios of above abnormal waves in EEG in FMT group were obviously lower than those in model group [the ratios of above abnormal waves in FMT group were respectively 9.1% (1/11), 9.1% (1/11), 18.2%(2/11)]. ③ Western Blot analysis showed that the protein expression of Iba-1 in cortex in model group obviously was higher than that in sham operation group (Iba-1/β-actin: 1.39±0.16 vs. 0.67±0.18, P < 0.05); the expression of Iba-1 in cortex tissue of FMT group was markedly lower than that in model group (Iba-1/β-actin: 0.51±0.14 vs. 1.39±0.16, P < 0.05). ④ Immunohistochemistry of Iba-1 in cortex analysis showed that there were no Iba-1 positive cells in the cortex in sham operation group; Iba-1 positive cells were found in the cortex in model group; the number of Iba-1 positive cells in FMT group was less than that in model group. Conclusion FMT can improve the construction of intestinal microbiota, and ameliorate the brain dysfunction in SAE.

Objective: To explore the virulence related risk factors based on the enterovirus A71 (EV-A71) genome. Methods: The pairwise distance of each section of gene between mild and fatal cases was analyzed. The ⅴ domain of 5′UTR from mild and fatal cases in this study were constructed. Amino acid sequences of EV-A71 were analyzed to find the potential virulence regions which were statistically different between fatal and mild cases. Results: The two EV-A71 genome sequences in this study belonged to C4a genotype with the genomic homology of 96.2%-97.5%. The nucleotides in the ⅴ domains of the 5 ′UTR of EV-A71 from mild and fatal cases were the same. Each gene of EV-A71 from 31 mild cases and 30 fatal cases shared high homology. A total of four potential virulence sites (2 A: R68 M、2C: K41R、3 A: T/V47 A and 3C: I158 V) which were significantly different between mild cases and fatal cases were obtained. Conclusions The four sites in the unstructured protein coding region might be related with the virulence of EV-A71.

Objective: To investigate the clinical value of endoscopic ultrasonography (EUS) and Multi-slice Spiral CT (MSCT) in the preoperativestaging of tumor(T) and lymph node (N) metastasis in patients with SiewertⅡand Ⅲ typeadenocarcinoma of esophagogastric junction(AEG). Methods: Clinical data of 145 Siewert Ⅱ and Ⅲ type AEG patientswithout preoperative chemoradiotherapy were retrospectively reviewed. Theyall received preoperative EUS and MSCT examination and underwent surgical resection, and the results of EUS and MSCT were compared with their postoperative pathologic staging. Results: The sensitivity, specificity, and accuracy of EUS for T stage in Siewert Ⅱ and Ⅲ type AEG were higher than those of MSCT. The total accuracy of EUS and MSCT were 90.3% and 63.5%, respectively, and the difference was statistically significant (χ²=29.52, P<0.01). The sensitivity of EUS for T1, T2 and T3 were 89.5%, 91.1% and 85.2%, respectively, which were significantly higher than 42.1%, 66.7% and 29.6% of MSCT (χ²=9.47, P<0.01 for T1; χ²=8.07, P<0.01 for T2; χ²=17.40, P<0.01 for T3). In addition, the total accuracy of EUS and MSCT for lymph node metastasis status of Siewert Ⅱ and Ⅲ type AEG were 75.9% and 64.8%, respectively, showing a statistically significant difference(χ²=4.23, P=0.04). The sensitivity of EUS for N1 and N2 were 82.1% and 79.2%, respectively, which were significantly higher than 53.6% and 60.4% of MSCT (χ²=5.24, P=0.02; χ²=4.48, P=0.03). There was no statistical significance for sensitivity of EUS and MSCT in N0 and N3 (P>0.05). Conclusion EUS diagnosis of T and N staging in Siewert Ⅱ/Ⅲ type AEG showed significantly greater performance than MSCT.

Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.

Objective:To investigate whether endogenous hydrogen sulfide (H2 S)was involved in the pathogenesis of osteoarthritis (OA)and its underlying mechanism,to detect H2 S and its synthases ex-pression in knee cartilage in patients diagnosed with different severity of OA,and to explore the transcrip-tion and expression of gene MMP-13 in chondrocytes treated with IL-1βor H2S.Methods:Synovial fluids of the in-patients with different severity of OA hospitalized in Peking University First Hospital were collected for measurement of H2 S content using methylene blue assay.Articular cartilages of the patients who underwent knee arthroplasty were collected for the cell culture of relatively normal chondrocytes.The chondrocytes were cultured to the P3 generation and H2 S molecular probes were used for detection of endogenous H2 S generation in the chondrocytes.Immunocytochemistry was used to detect the localization of H2 S synthases including cystathionine β-synthase (CBS),cystathionine-γ-lyase (CSE),and mercap-topyruvate sulfurtransferase (MPST)in OA chondrocytes.Western blot was used to quantify the protein expressions of CSE,MPST,and CBS in cartilage tissues of the patients who were diagnosed with OA and underwent knee arthroplasty.The relatively normal human chondrocytes were cultured to passage 3 and then divided into 4 groups for different treatments:(1 )the normal control group,no reagent was added;(2)the IL-1βgroup,5 μg/L of IL-1βwas added;(3)the IL-1β+H2S group,200 μmol/L of NaHS was added 30 min before adding 5 μg/L of IL-1β;(4)the H2 S group,200 μmol/L of NaHS was added. The transcription and expression of gene MMP-13 in chondrocytes of each group were determined with Real-time PCR and Western blot,respectively.And the total NF-κB p65 and phosphorylated NF-κB p65 in chondrocytes were detected with Western blot.Results:The content of H2 S in the synovial fluid of degenerative knee was (14.3 ±3.3)μmol/L.Expressions of endogenous H2 S and its synthases including CBS,CSE and MPST were present in the cytoplasm of chondrocytes.CSE protein expression in Grade 3 (defined by outerbridge grading)cartilage tissues was significantly increased as compared with that of Grade 1 cartilage tissues (1.67 ±0.09 vs.1.26 ±0.11,P<0.05).However,no significant difference of CBS or MPST expression among the different groups was observed.The expression of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (1 .87 ±0.67 vs.0.22 ± 0.10,P<0.05 ),and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (0.55 ±0.11 vs.1.87 ±0.67,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The transcription of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (31.40 ±0.31 vs.1.00 ±0.00,P<0.05), and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (24.41 ± 1.28 vs.31.40 ±0.31,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The total NF-κB p65 in the IL-1βgroup was significantly higher than that in the normal chondrocytes (2.13 ±0.08 vs.0.73 ±0.08,P<0.05),and that in the IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (1 .24 ±0.13 vs.2.13 ±0.08,P<0.05 ),and that in the H2 S group had no significant difference compared with that in the normal control group.The phosphorylated NF-κB p65 in IL-1βgroup was significantly higher than that in the normal chondrocytes (1.30 ±0.13 vs.0.19 ±0.04,P<0.05),and that in IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (0.92 ±0.26 vs.1.30 ±0.13,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.Conclusion:H2 S affected the cartilage degeneration by partly inhibiting the degradation of extracellular matrix.

Objective To analyze the vision-related quality of life (VRQL) and mental disorder in patients with primary open angle glaucoma (POAG) patients. Methods Ophthalmic examinations were carried out in 200 POAG participants from May, 2013 to April, 2016. Another 100 volunteers were enrolled as control group. The questionnaires included VRQL, linear rating scale (RS) and Hospital Anxiety and Depression Scale. Results The score of VRQL decreased significantly in the patients group (t=3.998, P<0.001), which mainly showed in dyslexia, dark adaptation, and driving (F>2.523, P<0.05). The RS score significantly decreased in the patients group (t=4.021, P<0.001). The detection rates of anxiety and depression were obviously higher in the patients group than in the control group. Conclusion Patients with POAG have disabilities in mental disorder, self-assessment and VRQL, which need seriously attention.