ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Objective:To study the effects of periodontitis on bone and tryptophan metabolism of gut microbiota in the context of estrogen deficiency.Methods:Thirty-two female C57BL6/J mice were randomly divided into four groups based on table of random numbers ( n=8 in each group): Sham group, in which mice were given sham surgery; Sham_Lig group, in which mice were given sham surgery and were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk threads at the fourth week; Ovx group, in which mice were given bilateral ovariectomy; Ovx_Lig group, in which mice were given bilateral ovariectomy and were induced to periodontitis at the fourth week. After 8 weeks of ligation, the mice of 4 groups were euthanized for collecting the samples of femur, tibia, mandible and skull. Those samples were scanned by micro-CT to measure the bone mineral density (BMD), bone volume versus total volume ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp). The cecum contents of 4 groups of mice were collected for gut microbiota 16S rRNA gene sequencing. The tryptophan and its metabolites in intestinal tracts were detected by liquid chromatography-mass spectrometry. Pearson correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and the content of tryptophan and its metabolites. Results:Femur BMD [(82.23±3.97) mg/cm 3], BV/TV [(9.25±1.37)%] and Tb.Th [(70.95±5.70) μm] in Ovx_Lig group were significantly lower than Ovx group [(96.30±3.76) mg/cm 3 ( P=0.004); (14.45±1.55)% ( P=0.022) and (87.58±8.02) μm ( P<0.001), respectively]. The β-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of Ovx_Lig group and Ovx group were obviously grouped. Linear discriminant analysis effect size (LEfSe) showed that Alistipes was the representative genus in Ovx_Lig group. The relative abundance of Alistipes in Ovx_Lig group [(0.42±0.14)%] were significantly higher than that in Ovx group [(0.17±0.05)%] ( t=4.45, P<0.001). Tryptophan metabolism analysis showed that the content of kynurenic acid [(531.12±158.60) ng/g] in Ovx_Lig group were significantly higher than that in Ovx group [(400.42±57.96) ng/g] ( t=2.19, P=0.046). And the content of indole-3-carbaldehyde [(383.37±144.06) ng/g] in Ovx_Lig group were significantly lower than Ovx group [(701.72±141.93) ng/g] ( t=4.45, P<0.001). Correlation analysis showed that relative abundance of Alistipes was positively correlated with kynurenic acid ( r=0.32, P=0.088), while negatively correlated with indole-3-carbaldehyde ( r=-0.32, P=0.088). Conclusions:Periodontitis can induce bone destruction of femur in estrogen-deficient mice, the mechanism of which may be related to Alistipes in gut and the tryptophan metabolites kynurenic acid and indole-3-carbaldehyde.

Objective To explore the characteristics of response inhibition of military university students during multitasking operation. Methods Repeated measures of ANOVA as well as distribution test were employed to explore how the performance of 127 military university students in Go/No-Go test was affected by simulated driving task. Results The test results of 127 participants showed that there was a interaction between the interference task and the Go trial proportion on the hit rate and false alarm rate,that is,no significant difference was observed between the 60％ and 40％ of trial proportion without interference task (both P>0.05),but the hit rate and false alarm rate in the 60％ trial proportion condition were significantly higher than those in the 40％ trial proportion condition under interference task (both P<0.01).In addition,significant main effects of interference task were observed on hit rate,false alarm rate,and discrimination index d' (all P<0.01),that is,the interference task reduced the hit rate and discrimination,but increased the false alarm rate.Moreover,individual differences existed in the discrimination index d' changes,and the participants were divided into easily disturbed group (n=23,18.11％),undisturbed group (n=20,15.75％),and intermediate group (n=84,66.14％) by adding or subtracting 1 standard deviation from the mean of the difference. Conclusion The interference tasks increase the psychological load of military university students during multitasking operation,and impair the response inhibition;and individual differences exist in response inhibition.

Wilson's disease (WD) is a rare autosomal recessive disorder with a complex pathogenesis involving multiple systems, multiple visceral organs, and the complex copper homeostasis regulation system within the body. The liver is the most common organ for copper deposition, and liver injury is the earliest and most common manifestation of WD; therefore, it is important to find an ideal animal model for WD research. By summarizing the animal models of WD commonly used in the world, this article systematically summarizes the background, liver and nervous manifestations, and application of different models and compares the characteristics of different animal models, so as to provide a reference for the application of various animal models of WD.

Stimulator of interferon genes (STING) is an important factor in the auto-immune response of our bodies.Considering the mechanism of activating CD8+ T cells after the activation of STING protein, the combination of STING agonists and immune checkpoint inhibitors for the treatment of tumor immunotherapy has good clinical application prospect.In this paper, the research progress of molecular types, mechanism of action and structural modifications of STING agonists were reviewed.The developing tendency were outlined to provide some references for further investigation.

Objective:To study the effects of salivary microbiota in patients with periodontitis on the tryptophan-aryl hydrocarbon receptor (AhR) signaling axis in mice with periodontitis and to provide theoretical basis as well as new ideas for the influences of periodontitis on systemic metabolism.Methods:Salivary microbiota of 12 healthy individuals and 14 patients with periodontitis were collected in Nanjing Stomatological Hospital, Medical School of Nanjing University from June to December of 2020. According to the random number table method, twenty-four mice were randomly divided into three groups: Sham group (control group), P group (periodontitis patients′ salivary microbiota group) and H group (periodontal healthy individuals′ salivary microbiota group). The maxillary second molars of all mice were treated with silk thread ligation to induce periodontitis. Phosphate buffer as well as salivary microbiota of periodontal healthy individuals and periodontitis patients were gavaged into periodontitis mice for 2 weeks. The expression of inflammatory factors in mice serum were detected by enzyme linked immunosorbent assay, and the expression of tryptophan and indole metabolites in intestinal tract and serum were detected by liquid chromatography-mass spectrometry. The expression of AhR in intestinal tract of mice was detected by immunohistochemistry and quantitative real time-PCR while gut microbiota constitution was detected by 16S rRNA gene sequencing. The remaining saliva samples of periodontitis patients and periodontal healthy individuals were applied to detect the expression of tryptophan and indole metabolites themselves.Results:The salivary microbiota of periodontitis patients could induce the expression of interleukin-1β [P group: (162.38±39.46) pg/ml, H group: (82.83±20.01) pg/ml; t=4.40, P=0.001) and tumor necrosis factor-α [P group: (361.16±123.90) pg/ml, H group: (191.66±106.87) pg/ml; t=2.54, P=0.030) in serum of periodontitis mice, and reduce the expression of AhR in colon (P group: 1.18±0.05, H group:1.83±0.47; t=3.09, P=0.015) and ileum (P group: 0.80±0.13, H group: 1.18±0.11; t=4.93, P=0.001). After gavage of salivary microbiota of periodontitis patients to the mice, tryptophan (P group: (18.1±3.8)×10 7, H group: (26.6±6.6)×10 7; t=2.49, P=0.037] and indole lactic acid [P group: (1.9±0.7)×10 7, H group: (3.7±0.6)×10 7; t=4.49, P=0.002) in serum of periodontitis mice were significantly decreased, but was relatively disorder in intestinal tract. However, the expressions of tryptophan and indole metabolites in saliva of periodontitis patients were higher than those of periodontal healthy individuals. There were significant differences in indole propionic acid [P group: (1 239.39±818.72) nmol/L, H group: (56.96±38.33) nmol/L; t=2.83, P=0.022]. What we find noteworthy was that the expressions of indolelactic acid metabolism in saliva, serum and intestinal were consistent, and salivary microbiota of periodontitis patients could reduce the relative abundance of indolelactic acid-producing bacteria in the gut, suggesting that the salivary microbiota of periodontitis patients might affect the expression of AhR through gut microbiota disorder and indolelactic acid downregulation. Conclusions:Salivary microbiota in patients with periodontitis may affect the systemic inflammatory state through down-regulating the expression of tryptophan-AhR signal axis.

Objective:To evaluate the efficacy of Q-switched 755 nm alexandrite laser combined with tranexamic acid in the treatment of facial melasma.Methods:According to the inclusion and exclusion criteria, the subjects were selected from female patients with melasma who visited the Department of Dermatology of Zhejiang Rongjun Hospital from June to December 2020, the patients were divided into group A, B and C according to the random number table. The study was conducted by half face self contrast method. Group A, lesions on the left side of the face were irradiated by Q-switched 755 nm alexandrite laser with the mode of 5 mm spot, 1.6 J/cm 2 energy, 70 ns pulse width(mode A) with an interval of two weeks for 6 sessions. Meanwhile, tranexamic acid serum was applied topically on the lesions twice a day for six months. Lesions on the right side of the face, as control side, tranexamic acid serum was used in the same way as above described. Group B, lesions on the left side of the face were irradiated by Q-switched 755 nm alexandrite laser for 6 sessions with the mode of 3 mm spot, 5.0 J/cm 2 energy, 150 μs pulse width(mode B) with an interval of two weeks for 6 sessions. Meanwhile, tranexamic acid serum was applied topically on the lesions twice a day for six months. The treatment of right side of face as control side was the same as group A. The treatment method and postoperative treatment of the left face in group C were the same as those in group A left face. The treatment method and postoperative treatment of the right side face were the same as those of the left side face of group B. The treatment effect was evaluated 12 weeks after the end of laser treatment. (1) Assessment of Melasma Area and Severity Index (MASI), the score ranges from 0 to 48, with higher scores indicating more severe lesions. (2) Physician Global Assessment(PGA), the score ranged from 0 to 6, and the higher the score, the more melasma remained. (3) The patient satisfaction rate was the percentage of the total number of patients with very satisfied and satisfied cases. Measurement data to (Mean±SD), the MASI score and PGA score were compared by paired sample t-test, patient satisfaction is using chi-square test, P<0.05 was considered statistically significant. Results:A total of 90 patients were enrolled, and they were divided into A, B and C groups according to the ratio of 1∶1∶1, with 30 patients in each group. The age of patients in group A, B and C were (33.0±5.8) years, (32.3±7.2) years and (32.9±6.5) years, respectively ( P>0.05), the disease duration was (3.5±2.3) years, (3.3±1.9) years, (3.5±1.5) years, respectively ( P>0.05). Assessing the efficacy of 12 weeks after the last laser treatment: (1) MASI. The scores of both sides of the face in group A after treatment were lower than those before treatment ( P< 0.01 or <0.05), and the scores of the left side after treatment (9.67±4.10) were significantly lower than those of the right side (18.13±7.67) ( P<0.01). The scores of both sides of the face in group B after treatment were significantly lower than those before treatment ( P<0.01 or 0.05), and the scores of the left side (9.97±3.74) were significantly lower than those of the right side (18.01±7.17) after treatment ( P<0.01). The scores of both sides of the face in group C after treatment were significantly lower than those before treatment ( P<0.01), and the scores of the left side of the face after treatment (9.92±4.11) were higher than those of the right side (7.95±3.27) ( P<0.05), the effect of laser treatment in mode B was better than that in mode A. (2) PGA. The score of the left side of the face in group A was (1.63±1.32), lower than the right side of the face (2.97±1.50) ( P<0.01). The left side score of group B was (1.27 ± 1.02), which was lower than that of the right side (2.87±1.46) ( P<0.01). The left side score of group C was (1.97±1.16), higher than that of the right side (1.27±1.02) ( P<0.05). It shows that the therapeutic effect of mode B laser is better than that of mode A laser. (3) Patient satisfaction rate. The left side satisfaction rate of group A was 67% (20/30), higher than that of right side 37% (11/30) ( P<0.05). In group B, the satisfaction rate of the left side was 73% (22/30), higher than that of the right side 47% (14/30) ( P<0.05). The satisfaction rate of the left side in group C was 53% (16/30), which was lower than that of the right side 80%(24/30), indicating that the satisfaction rate of the mode B laser treatment side was higher than that of the mode A ( P<0.05). Conclusions:The treatment of Q-switched 755 nm alexandrite laser combined with topical tranexamic acid can significantly improve facial melasma, and the treatment mode with 3 mm spot, 5.0 J/cm 2 energy density, 150 μs pulse width parameters is recommended.

Objective:To evaluate the efficacy of Q-switched 755 nm alexandrite laser combined with tranexamic acid in the treatment of facial melasma.Methods:According to the inclusion and exclusion criteria, the subjects were selected from female patients with melasma who visited the Department of Dermatology of Zhejiang Rongjun Hospital from June to December 2020, the patients were divided into group A, B and C according to the random number table. The study was conducted by half face self contrast method. Group A, lesions on the left side of the face were irradiated by Q-switched 755 nm alexandrite laser with the mode of 5 mm spot, 1.6 J/cm 2 energy, 70 ns pulse width(mode A) with an interval of two weeks for 6 sessions. Meanwhile, tranexamic acid serum was applied topically on the lesions twice a day for six months. Lesions on the right side of the face, as control side, tranexamic acid serum was used in the same way as above described. Group B, lesions on the left side of the face were irradiated by Q-switched 755 nm alexandrite laser for 6 sessions with the mode of 3 mm spot, 5.0 J/cm 2 energy, 150 μs pulse width(mode B) with an interval of two weeks for 6 sessions. Meanwhile, tranexamic acid serum was applied topically on the lesions twice a day for six months. The treatment of right side of face as control side was the same as group A. The treatment method and postoperative treatment of the left face in group C were the same as those in group A left face. The treatment method and postoperative treatment of the right side face were the same as those of the left side face of group B. The treatment effect was evaluated 12 weeks after the end of laser treatment. (1) Assessment of Melasma Area and Severity Index (MASI), the score ranges from 0 to 48, with higher scores indicating more severe lesions. (2) Physician Global Assessment(PGA), the score ranged from 0 to 6, and the higher the score, the more melasma remained. (3) The patient satisfaction rate was the percentage of the total number of patients with very satisfied and satisfied cases. Measurement data to (Mean±SD), the MASI score and PGA score were compared by paired sample t-test, patient satisfaction is using chi-square test, P<0.05 was considered statistically significant. Results:A total of 90 patients were enrolled, and they were divided into A, B and C groups according to the ratio of 1∶1∶1, with 30 patients in each group. The age of patients in group A, B and C were (33.0±5.8) years, (32.3±7.2) years and (32.9±6.5) years, respectively ( P>0.05), the disease duration was (3.5±2.3) years, (3.3±1.9) years, (3.5±1.5) years, respectively ( P>0.05). Assessing the efficacy of 12 weeks after the last laser treatment: (1) MASI. The scores of both sides of the face in group A after treatment were lower than those before treatment ( P< 0.01 or <0.05), and the scores of the left side after treatment (9.67±4.10) were significantly lower than those of the right side (18.13±7.67) ( P<0.01). The scores of both sides of the face in group B after treatment were significantly lower than those before treatment ( P<0.01 or 0.05), and the scores of the left side (9.97±3.74) were significantly lower than those of the right side (18.01±7.17) after treatment ( P<0.01). The scores of both sides of the face in group C after treatment were significantly lower than those before treatment ( P<0.01), and the scores of the left side of the face after treatment (9.92±4.11) were higher than those of the right side (7.95±3.27) ( P<0.05), the effect of laser treatment in mode B was better than that in mode A. (2) PGA. The score of the left side of the face in group A was (1.63±1.32), lower than the right side of the face (2.97±1.50) ( P<0.01). The left side score of group B was (1.27 ± 1.02), which was lower than that of the right side (2.87±1.46) ( P<0.01). The left side score of group C was (1.97±1.16), higher than that of the right side (1.27±1.02) ( P<0.05). It shows that the therapeutic effect of mode B laser is better than that of mode A laser. (3) Patient satisfaction rate. The left side satisfaction rate of group A was 67% (20/30), higher than that of right side 37% (11/30) ( P<0.05). In group B, the satisfaction rate of the left side was 73% (22/30), higher than that of the right side 47% (14/30) ( P<0.05). The satisfaction rate of the left side in group C was 53% (16/30), which was lower than that of the right side 80%(24/30), indicating that the satisfaction rate of the mode B laser treatment side was higher than that of the mode A ( P<0.05). Conclusions:The treatment of Q-switched 755 nm alexandrite laser combined with topical tranexamic acid can significantly improve facial melasma, and the treatment mode with 3 mm spot, 5.0 J/cm 2 energy density, 150 μs pulse width parameters is recommended.

Objective:To explore the effects of scenario simulation combined with case-based learning (CBL) teaching method on the operation skills, learning initiative and family satisfaction of pediatric nursing students.Methods:In the study, 51 nursing students who interned in Bengbu First People's Hospital from March to November in 2019 were selected as the control group, having the traditional teaching method; another 51 nursing students interned from March to November in 2020 were selected as the research group, taking the scenario simulation combined with CBL teaching method. The theoretical knowledge and operation skills of the two groups of nursing students were assessed, the learning initiative and various abilities were evaluated by using the relevant scales, and the nursing students' satisfaction with teaching was investigated. SPSS 22.0 was used for t test and chi-square test. Results:The theoretical knowledge and operation skill scores of nursing students in the study group were significantly higher than those in the control group ( P<0.05). The scores of each dimension and total score of learning initiative of nursing students in the study group were higher than those in the control group [(68.71±9.03) vs. (50.21±9.86)], including integrating theory with practice [(8.06±1.13) vs. (6.12±1.54)], learning ability practice [(8.15±1.18) vs. (6.53±1.37)], interpersonal communication ability [(8.13±1.07) vs. (6.28±1.39)], clinical thinking ability practice [(8.04±1.26) vs. (5.97±1.42)], ability to analyze and solve problems [(8.46±0.97) vs. (6.51±1.25)]. The scores of various abilities and overall satisfaction with teaching in the research group were significantly higher than those in the control group ( P<0.05). Conclusion:The implementation of scenario simulation combined with CBL teaching method for pediatric nursing students can improve their scores of theoretical knowledge and operational skills, enhance their learning initiative and abilities, and improve their satisfaction with teaching.

Liver fibrosis is the initial stage of the development of various chronic liver diseases into liver cirrhosis and is a reversible process. As a subset of extracellular vesicles that can carry active substances such as proteins, lipids, and RNA, exosomes are involved in intercellular signal communication and have attracted more and more attention in recent years. Studies have shown that non-coding RNAs in exosomes play an important role in the development and progression of liver fibrosis. This article discusses the mechanism of action of exosome long non- coding RNAs (including MALAT1, H19, GAS5, MEG3, PVT1, and P21), exosome short non-coding RNAs (including micro-RNA, small nucleolus RNA, PIWI-interacting RNA, and small interference RNA), and exosome circular RNA in the development and progression of liver fibrosis, and it is concluded that exosomes from different sources (such as hepatocytes and cholangiocytes) carrying non-coding RNAs mainly affect the activation, proliferation, migration, and transformation of hepatic stellate cells. In-depth studies of exosome non-coding RNAs in the future are expected to find potential new targets for the treatment of liver fibrosis.