Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective:To investigate the effectiveness and feasibility of a 3D U-Net in conjunction with a three-phase CT image segmentation model in the automatic segmentation of GTVnx and GTVnd in nasopharyngeal carcinoma.Methods:A total of 645 sets of computed tomography (CT) images were retrospectively collected from 215 nasopharyngeal carcinoma cases, including three phases: plain scan (CT), contrast-enhanced CT (CTC), and delayed CT (CTD). The dataset was grouped into a training set consisting of 172 cases and a test set comprising 43 cases using the random number table method. Meanwhile, six experimental groups, A1, A2, A3, A4, B1, and B2, were established. Among them, the former four groups used only CT, only CTC, only CTD, and all three phases, respectively. The B1 and B2 groups used phase fine-tuning CTC models. The Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) served as quantitative evaluation indicators.Results:Compared to only monophasic CT (group A1/A2/A3), triphasic CT (group A4) yielded better result in the automatic segmentation of GTVnd (DSC: 0.67 vs. 0.61, 0.64, 0.64; t = 7.48, 3.27, 4.84, P < 0.01; HD95: 36.45 vs. 79.23, 59.55, 65.17; t = 5.24, 2.99, 3.89, P < 0.01), with statistically significant differences ( P < 0.01). However, triphasic CT (group A4) showed no significant enhancement in the automatic segmentation of GTVnx compared to monophasic CT (group A1/A2/A3) (DSC: 0.73 vs. 0.74, 0.74, 0.73; HD95: 14.17 mm vs. 8.06, 8.11, 8.10 mm), with no statistically significant difference ( P > 0.05). For the automatic segmentation of GTVnd, group B1/B2 showed higher automatic segmentation accuracy compared to group A1 (DSC: 0.63, 0.63 vs. 0.61, t = 4.10, 3.03, P<0.01; HD95: 58.11, 50.31 mm vs. 79.23 mm, t = 2.75, 3.10, P < 0.01). Conclusions:Triphasic CT scanning can improve the automatic segmentation of the GTVnd in nasopharyngeal carcinoma. Additionally, phase fine-tuning models can enhance the automatic segmentation accuracy of the GTVnd on plain CT images.

Objective To observe the value of three-dimensional ultrasound virtual organ computer-aided analysis(VOCAL)technique for measuring choroid plexus volume(CPV)and lateral ventricle volume(LVV)in normal fetus of 11-13+6 gestational weeks.Methods Three-dimensional ultrasonic data of 428 normal singletons at 11-13+6 gestational weeks were retrospectively analyzed.The fetuses were divided into 11-11+6 weeks group(n=77),12-12+6 weeks group(n=225)and 13-13+6 weeks group(n=126).Fetal CPV,LVV and CPV/LVV ratio were measured and calculated using VOCAL technique and compared between groups.Pearson correlation analysis was performed to observe the correlations of CPV,LVV,CPV/LVV ratio with crown-rump length(CRL).Results Significant differences of CPV,LVV and CPV/LVV ratio were found among groups(all P＜0.05).Among 11-11+6 weeks group,12-12+6 weeks group and 13-13+6 weeks group,CPV and LVV increased progressively,while CPV/LVV ratio decreased progressively(all adjusted P＜0.05).During 11-13+6 gestational weeks,CPV and LVV were both highly positively correlated with CRL(r=0.904,0.929,both P＜0.05),while CPV/LVV ratio was highly negatively correlated with CRL(r=-0.893,P＜0.05).Conclusion Three-dimensional ultrasound VOCAL technique was feasible for measuring CPV and LVV in normal fetus of 11-13+6 gestational weeks.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective:To establish a method of serum detection by Raman spectroscopy for the diagnosis of gastric cancer.Methods:Between April and November 2019, 110 patients with gastric cancer [73 males, 37 females, age (57.4±10.3) years] and 74 patients with colorectal cancer [48 males and 26 females, aged (58.3±12.2) years] were collected at the First Affiliated Hospital of Army Military Medical University, along with 100 healthy subjects [59 males and 41 females, aged (55.6±10.61) years] during the same period. Fasting venous blood serum samples were collected from the subjects. A Raman spectrometer XploRA PLUS was used in this experiment, with an excitation light source of 532 nm, a field of view of 100 times, and a spectrum range of 200-2 000 cm -1, etc. The serum samples were detected by nondestructive and non-contact rapid detection, and the Raman spectra of serum samples were collected. Using the Raman spectrum acquisition and processing supporting software LabSpec6 to smooth, baseline, and normalize the obtained Raman spectrum. Multivariate statistical analysis software SIMCA14.1 were applied to import and analyze the obtained Raman spectrum data by principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and other methods for statistical analysis. An operating characteristic curve (ROC) was constructed to evaluate the model analysis effect between serum samples of healthy people and those with gastric cancer. Serum samples from the colorectal cancer group were used to verify the reliability of the model. Results:Six Raman peaks with good repeatability were detected in serum samples in health and gastric cancer group, and peaks were located at 1 001.17, 1 154.63, 1 337.89, 1 446.85, 1 515.33, and 1 658.34 cm -1, respectively. Raman intensities at six Raman peaks were significantly different between healthy and gastric cancer groups. At the displacement of 1 001.17, 1 154.63, and 1 515.33 cm -1, the Raman intensity in the healthy group was higher than that in the gastric cancer group. At 1 337.89, 1 446.85, and 1 658.34 cm -1 displacement, the Raman intensity of the gastric cancer group was higher than that of the healthy group. An OPLS-DA model was constructed to analyze the serum samples of the healthy group and the gastric cancer group. In the model, R 2 is the fitting power, and Q 2 is the predictive ability. The closer the values of R 2 and Q 2 are to 1, the better the performance of the model, and the obtained model's R 2X(cum)=0.809, R 2Y(cum)=0.819, Q 2(cum)=0.758. ROC characteristic curve was drawn based on the OPLS-DA model. The area under the curve (AUC) of the gastric cancer group was 0.998. Six peaks with good repeatability were detected in the serum Raman spectra of gastric cancer stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ, which were located at the displacement of 1 001.85, 1 155.07, 1 338.36, 1 445.75, 1 515.92, and 1 657.68 cm -1, respectively, and at the displacement of 1 155.07 and 1 515.92 cm -1. The Raman intensity of gastric cancer stage Ⅳwas significantly higher than that of gastric cancer stages Ⅰ, Ⅱ, and Ⅲ. Conclusions:According to the model reliability verification, the healthy group, gastric cancer group and colorectal cancer group can also be effectively separated based on OPLS-DA results; it showed a good performance in separating the healthy group from the gastric cancer group. It is possible to detect serum samples from healthy people and gastric cancer patients unlabeled by combining Raman spectroscopy and the OPLS-DA method in multivariate statistics.

Objective:To evaluate the value of improved pulmonary ultrasonography in the follow-up assessment of lung damage in patients who recovered from corona virus disease 2019(COVID-19).Methods:Twenty-two patients who were cured of COVID-19 in Quanzhou First Hospital from January to May 2020 were randomly selected and divided into 7 mild cases, 12 moderate cases and 3 severe cases according to the first high-resolution CT (HRCT) at admission. Six months after recovery, modified lung ultrasonography and HRCT were used prospectively to assess the lung damage and evaluate the correlation and consistency between the two techniques.Results:①There were significant differences in lung damage between the mild group and the moderate group, severe group (all P<0.05), while there was no significant difference between the moderate group and severe group ( P>0.05). ②There was good consistency between the improved lung ultrasound examination and HRCT (Kappa=0.776, P<0.001). ③There was a positive correlation between the score of improved pulmonary ultrasound examination and HRCT Warrick score ( r=0.755, P<0.001). Conclusions:Improved pulmonary ultrasonography can be used as a priority in the evaluation of pulmonary damage follow-up in patients with COVID-19 recovery, reducing the use of CT, and providing favorable evidence for further clinical management.

Objective:To explore a fast method to identify and confirm suspected clonorchis sinensis infection.Methods:For suspected clonorchis sinensis infection, the clonorchiasis serum antibody was detected first with ELISA. If the antibody was positive, the fecal examination for eggs was performed. If the fecal examination was negative, duodenal drainage under gastroscopy was recommended to detect eggs from the drainage fluid.Results:A total of 126 patients met the requirements and aged 54.14±13.33 (24- 87). There were 83 cases (65.87%, 83/126) with eggs positive in the drainage fluid, of which 53 cases were male, aged 55.91±11.47 (30-86), and 30 cases female, aged 55.87± 13.85(30-87). There was no significant difference in age between males and females( P>0.05). The time of catheterization (T1) of 126 cases was 3.79 ±1.45 min. The time of drainage (T2) of 126 cases was 31.39 ±14.29 min. There was no significant difference in T1 or T2 between the positive group and the negative group( P>0.05). The detection rates of eggs were 91.57% (76 cases) in intrahepatic bile duct drainage, 81.93% (68 cases) in the bile-cyst juice and 75.90% (63 cases) in the common bile duct fluid. No serious adverse reactions occurred during or after the operation. Conclusion:The detection rate of clonorchiosis sinensis can be effectively improved by the combination of clonorchiasis serum antibody test and gastroscopy-guided duodenal drainage.

Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP₁₈ column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, c_max was (9 680±3725) and (9 310±1 645) ng/ml; t_max was (1.25±0.67) and (0.011±0.017) h, AUC_0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC_0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t_1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.

Objective:To evaluate the diagnostic value of refined transthoracic lung ultrasound(TLUS) scoring method in interstitial lung diseases(ILD).Methods:The TLUS was performed in 39 ILD patients in respiratory department and immunology department of the Second Affiliated Hospital of Fujian Medical University from March 2019 to February 2020. The ultrasonic recordings were evaluated by Buda ultrasound scoring method and refined ultrasound scoring method. The diagnostic efficacies of the refined ultrasound scoring method, Buda ultrasound scoring method and high resolution computed tomography(HRCT) scoring method for ILD were analyzed. The correlations between refined ultrasound score and Buda ultrasound score/HRCT score were evaluated. The difference of diagnostic efficacy between refined ultrasound scoring method and Buda ultrasound scoring method were analyzed in different severity of ILD. Then, the HRCT Warrick scoring method was used as the criterion to judge the severity of ILD, and the receiver operator characteristic (ROC) curve was plotted to predict the cutoff values of the fefined ultrasound score for different degrees of ILD.Results:①The sensitivity of the refined ultrasound scoring method in diagnosing ILD was 92.3%, specificity was 92.3%, area under ROC curve(AUC)=0.978, 95% CI=0.941-1.000. The sensitivity of Buda ultrasound scoring method in diagnosing ILD was 87.2%, specificity was 87.2%, AUC=0.950, 95% CI=0.892-1.000. The sensitivity of HRCT scoring method in diagnosing ILD was 97.4%, specificity was 97.4%, AUC=0.999, 95% CI=0.994-1.000. ②The correlations between the refined ultrasound score, the HRCT Warrick score and the Buda ultrasound score were high ( r=0.929, 0.920, 0.862 respectively, P<0.001). ③The values of refined ultrasound scoring method and Buda ultrasound scoring method consistently and significantly increased with the increasing severity of ILD. With regards to the former one, there were significant differences among mild group, moderate group and severe group ( P<0.05). ④The ROC curve confirmed that refined ultrasound score cut-off points for predicting mild and severe interstitial lung diseases, were 34 [sensitivity of 100%, specificity of 87.5% respectively, AUC=0.891, 95% CI=0.686-1.000] and 64.5 [sensitivity of 91.3%, specificity of 87.5% respectively, AUC=0.954, 95% CI=0.877-1.000]. Conclusions:The severity of the interstitial lung diseases could be evaluated by the refined ultrasound scoring method, which is useful in the semi-quantitative evaluation of ILD.