ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective:To construct a deep learning model based on YOLOV8-Seg algorithm to conduct automatic segmentation for the central gland(CG)and peripheral zone(PZ)of prostate,so as to provide a reliable basis for clinical diagnosis and treatment.Methods:The sequence data of T2-weighted imaging(T2WI)of horizontal relaxation time of 158 patients were selected from a public data set of magnetic resonance imaging(MRI)for prostate MRI,which was provided by the Charité University Hospital in Berlin,were selected.The all data were divided into a training set(109 cases),a validation set(16 cases),and a test set(33 cases)as the ratio of 7 to1 to 2.A lightweight asymmetric decoupled head(LADH)structure and the large kernel UniRepLKNetBlock module were integrated into the YOLOV8-Seg algorithm to enhance the capabilities of model's extraction feature,and the new model was named as YOLOV8-URLK.The assessment model with mean Average Precision(mAP),Dice Similarity Coefficient(DSC),95%Hausdorff Distance(HD95),and Average Surface Distance(ASD)was adopted to segment performance of the detection at prostate CG and PZ.Comparative experiments were conducted among that and YOLOV8-Seg,TransU-Net,and U-Net network,so as to validate the effectiveness of YOLOV8-URLK for detection and segmentation at prostate zone.Results:On the test set,the mAP@0.5(box)of YOLOV8-URLK model was 0.878,and the mean Dice coefficients,the mean HD95 values and the ASD values of that at CG and PZ were respectively(0.867,17.123 and 1.461)and(14.902,0.898 and 1.112).On the test set,the mAP@0.5(box)of YOLOV8-Seg model was 0.860,and the mean Dice coefficients of that at CG and PZ were 0.851 and 0.884,the mean HD95 values of that at them were 19.174 and 15.298,and ASD values of that at them were 1.781 and 1.219,respectively.On test set,the mean Dice coefficients of TransU-Net model at CG and PZ were 0.864 and 0.824,and the mean HD95 values of that at them were 18.134 and 19.402,and ASD values of that at them were 1.698 and 1.717,respectively.On the test set,the mean Dice coefficients of the U-Net model at CG and PZ were 0.857 and 0.690,and the mean HD95 values of that at them were 18.976 and 26.934,and ASD values of that at them were 1.753 and 2.135.The YOLOV8-URLK model can better reappear the segmentation trend of manual annotations.Conclusion:The YOLOV8-URLK model demonstrates higher precision in the detection and segmentation of MRI images of prostate,which were superior to YOLOV8-Seg,TransU-Net and U-Net.It can enhance the efficiency of the detection and segmentation.

Objective:To construct a deep learning model based on YOLOV8-Seg algorithm to conduct automatic segmentation for the central gland(CG)and peripheral zone(PZ)of prostate,so as to provide a reliable basis for clinical diagnosis and treatment.Methods:The sequence data of T2-weighted imaging(T2WI)of horizontal relaxation time of 158 patients were selected from a public data set of magnetic resonance imaging(MRI)for prostate MRI,which was provided by the Charité University Hospital in Berlin,were selected.The all data were divided into a training set(109 cases),a validation set(16 cases),and a test set(33 cases)as the ratio of 7 to1 to 2.A lightweight asymmetric decoupled head(LADH)structure and the large kernel UniRepLKNetBlock module were integrated into the YOLOV8-Seg algorithm to enhance the capabilities of model's extraction feature,and the new model was named as YOLOV8-URLK.The assessment model with mean Average Precision(mAP),Dice Similarity Coefficient(DSC),95%Hausdorff Distance(HD95),and Average Surface Distance(ASD)was adopted to segment performance of the detection at prostate CG and PZ.Comparative experiments were conducted among that and YOLOV8-Seg,TransU-Net,and U-Net network,so as to validate the effectiveness of YOLOV8-URLK for detection and segmentation at prostate zone.Results:On the test set,the mAP@0.5(box)of YOLOV8-URLK model was 0.878,and the mean Dice coefficients,the mean HD95 values and the ASD values of that at CG and PZ were respectively(0.867,17.123 and 1.461)and(14.902,0.898 and 1.112).On the test set,the mAP@0.5(box)of YOLOV8-Seg model was 0.860,and the mean Dice coefficients of that at CG and PZ were 0.851 and 0.884,the mean HD95 values of that at them were 19.174 and 15.298,and ASD values of that at them were 1.781 and 1.219,respectively.On test set,the mean Dice coefficients of TransU-Net model at CG and PZ were 0.864 and 0.824,and the mean HD95 values of that at them were 18.134 and 19.402,and ASD values of that at them were 1.698 and 1.717,respectively.On the test set,the mean Dice coefficients of the U-Net model at CG and PZ were 0.857 and 0.690,and the mean HD95 values of that at them were 18.976 and 26.934,and ASD values of that at them were 1.753 and 2.135.The YOLOV8-URLK model can better reappear the segmentation trend of manual annotations.Conclusion:The YOLOV8-URLK model demonstrates higher precision in the detection and segmentation of MRI images of prostate,which were superior to YOLOV8-Seg,TransU-Net and U-Net.It can enhance the efficiency of the detection and segmentation.

Objective To compare the different intervention effect of aerobic exercise or complex poly-saccharide supplement on gut microbiota(GM),GM-related metabolic pathway genes,as well as fat and weight losing of obese rats induced by high-fat diet. Methods Thirty-two male Sprague-Dawley rats were randomly divided into a control group,an obesity control(OC) group,an aerobic exercise (AE) group and a complex polysaccharide intervention(CPI) group,each of 8. The AE group was giv-en moderate intensity treadmill aerobic training for 6 weeks,while the CPI group underwent plant poly-saccharide gavage for the same period of time. Morphological indicators were measured and recorded,serum regulators of lipid metabolism were collected,and feces were collected for metagenomic sequenc-ing and analysis. Results(1) Before the intervention,the body weight of group OC was significantly higher than the control group(P<0.01). However,after 6-week aerobic exercise,the body weight and Lee's index of group OC reduced significantly(P<0.05). (2) The concentrations of peroxisome prolifera-tor-activated receptor γ(PPAR-γ) and leptin(LEP) in serum of the OC group were significantly high-er than the control group(P<0.001),but that of lipoprotein lipase(LPL) was significantly lower than the control group(P<0.001). The serum concentrations of PPAR-γ in group AE were significantly low-er than group OC(P<0.01),while those of PPAR-γ and LEP in group CPI were significantly lower than group OC(P<0.001). (3) The abundance of Akkermansia mucinphila,Alistipes finegoldii,Bacteroides ovatus and Gram-negative bacterium cL10-2b-4 in group OC was significantly lower than the control group(P<0.05),with that of Prevotella copri in group AE significantly higher than group OC and that of Helicobacter rodentium significantly lower than the latter(P<0.05). Moreover,the abundance of Bifido-bacterium animalis in group CPI was significantly higher than group OC,while that of Alistipes shahii was significantly lower than the latter(P<0.05). (4) Compared with the control group,the obese group was significantly enriched in Vibrio cholerae pathogenic cycle,Staphylococcus aureus infection and vari-ous types of N-glycan biosynthesis related genes. Moreover,the abundance of salmonella infection and N-glycan biosynthesis-related genes in group AE was significantly lower than group OC(P<0.05),and that of Vibrio cholerae disease-cycle related genes in group CPI was significantly lower than group OC (P<0.05). Conclusion The imbalance in the gut microbiota structure,and the abnormal expression of related metabolic pathway genes both play important roles in the phenotype changes of high-fat diet in-duced rats,which can be effectively relieved by aerobic exercise and complex polysaccharide gavage. However,there are obvious differences in the effects and possible mechanisms between the above two intervention methods.

Objective To compare the different intervention effect of aerobic exercise or complex poly-saccharide supplement on gut microbiota(GM),GM-related metabolic pathway genes,as well as fat and weight losing of obese rats induced by high-fat diet. Methods Thirty-two male Sprague-Dawley rats were randomly divided into a control group,an obesity control(OC) group,an aerobic exercise (AE) group and a complex polysaccharide intervention(CPI) group,each of 8. The AE group was giv-en moderate intensity treadmill aerobic training for 6 weeks,while the CPI group underwent plant poly-saccharide gavage for the same period of time. Morphological indicators were measured and recorded,serum regulators of lipid metabolism were collected,and feces were collected for metagenomic sequenc-ing and analysis. Results(1) Before the intervention,the body weight of group OC was significantly higher than the control group(P<0.01). However,after 6-week aerobic exercise,the body weight and Lee's index of group OC reduced significantly(P<0.05). (2) The concentrations of peroxisome prolifera-tor-activated receptor γ(PPAR-γ) and leptin(LEP) in serum of the OC group were significantly high-er than the control group(P<0.001),but that of lipoprotein lipase(LPL) was significantly lower than the control group(P<0.001). The serum concentrations of PPAR-γ in group AE were significantly low-er than group OC(P<0.01),while those of PPAR-γ and LEP in group CPI were significantly lower than group OC(P<0.001). (3) The abundance of Akkermansia mucinphila,Alistipes finegoldii,Bacteroides ovatus and Gram-negative bacterium cL10-2b-4 in group OC was significantly lower than the control group(P<0.05),with that of Prevotella copri in group AE significantly higher than group OC and that of Helicobacter rodentium significantly lower than the latter(P<0.05). Moreover,the abundance of Bifido-bacterium animalis in group CPI was significantly higher than group OC,while that of Alistipes shahii was significantly lower than the latter(P<0.05). (4) Compared with the control group,the obese group was significantly enriched in Vibrio cholerae pathogenic cycle,Staphylococcus aureus infection and vari-ous types of N-glycan biosynthesis related genes. Moreover,the abundance of salmonella infection and N-glycan biosynthesis-related genes in group AE was significantly lower than group OC(P<0.05),and that of Vibrio cholerae disease-cycle related genes in group CPI was significantly lower than group OC (P<0.05). Conclusion The imbalance in the gut microbiota structure,and the abnormal expression of related metabolic pathway genes both play important roles in the phenotype changes of high-fat diet in-duced rats,which can be effectively relieved by aerobic exercise and complex polysaccharide gavage. However,there are obvious differences in the effects and possible mechanisms between the above two intervention methods.

Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.

Objective:To clarify the clinical significance, diagnostic and prognostic values of circular RNA circ_0141633 and circ_0008234 in peripheral blood of pancreatic cancer, and analyze their impact on the biological function of pancreatic cancer cells.Methods:The peripheral blood samples of 97 pancreatic cancer patients and 71 healthy controls were collected, and the expression of circ_0141633 and circ_0008234 was analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). The relationships between the expression of circ_0141633 and circ_0008234 and clinicopathological characteristics and prognosis of pancreatic cancer were analyzed by chi-square test, K-M survival curves and Cox proportional hazards regression model. The area under curve (AUC), sensitivity and specificity of circ_0141633 and circ_0008234 in the diagnosis of pancreatic cancer were analyzed by receiver operating characteristic (ROC) curve. The effects of circ_0141633 and circ_0008234 on the proliferation, migration, invasion and epithelial mesenchymal transformation (EMT) of Bxpc-3 cells were analyzed by methyl thiazolyl tetrazolium (MTT) method, cell scratch test, Transwell invasion and Western blot.Results:The expression of circ_0141633 and circ_0008234 in peripheral blood of pancreatic cancer patients was higher than those of healthy controls (all P<0.05). High expression of circ_0141633 and circ_0008234 was associated with higher clinical stage, lymph node metastasis and venous invasion, and were independent risk factors for poor prognosis in pancreatic cancer (all P<0.05). The overall survival rate of patients with high expression of circ_0141633 and circ_0008234 was significantly lower than that of patients with low expression of circ_0141633 and circ_0008234 (all P<0.05). The AUC of circ_0141633, circ_0008234, the combination of circ_0141633 and circ_0008234, CA19-9 in the diagnosis of pancreatic cancer was 0.70, 0.67, 0.88 and 0.82, with sensitivity of 64.32%, 60.79%, 78.22% and 73.97%, respectively. The specificity was 68.54%, 65.46%, 81.65% and 79.41%, respectively. The diagnostic efficiency of combination was superior to CA19-9, circ_0141633 and circ_0008234 alone (all P<0.05). Interfering with circ_0141633 and circ_0008234 alone could inhibit the proliferation, migration, invasion and EMT of Bxpc-3 cells, and the above inhibitory effect was more obvious after interfering with both of circ_0141633 and circ_0008234 (all P<0.05). Conclusions:The high expression of circ_0141633 and circ_0008234 in peripheral blood could be used as potential diagnostic and prognostic biomarkers of pancreatic cancer, and could promote the progression of pancreatic cancer.

Objective:To investigate the clinical features of adenoviral encephalitis (AE), and to provide reference for clinical diagnosis and treatment of adenoviral encephalitis.Methods:From January 2012 to December 2020, 1 185 cerebrospinal fluid (CSF) samples of hospitalized children with suspected central nervous system infection in the Second Affiliated Hospital of Shantou University Medical College were collected for the detection of 22 common respiratory pathogens and common pathogens for encephalitis by polymerase chain reaction. Records of patients with adenovirus positive in CSF were reviewed and relevant clinical manifestations, laboratory tests and imaging examination results were collected for analysis.Results:Among 1 185 CSF samples, 242 samples were positive for viral nucleic acid, with detection rate of 20.4%, including 1.9%(23/1 185) of adenovirus. As for 23 children diagnosed with AE, 18 were male, five were female, with the age of (44.8±35.9) months, ranging from two months and 19 days to 10 years. Of 23 children, 21(91.3%) presented with fever, followed by convulsions (16 cases, 69.6%), headache (four cases, 17.4%), vomiting (11 cases, 47.8%), consciousness change (11 cases, 47.8%) and emotion disturbance (three cases, 13.0%). Among 23 children, eight cases had white blood cell counts (WBC) of (6 to <10)×10 9/L, 10 cases had WBC of (10 to 20)×10 9/L and the white blood cell classification was mainly neutrophils (21 cases, 91.3%), and C reactive protein of 20 cases (87.0%) was in the normal range. Cerebrospinal fluid examination showed that WBC were less than 15×10 6/L in 20 cases (87.0%), and WBC ≥15×10 6/L in three cases, which were up to 500×10 6/L; the protein of 19 cases was in the normal range, the glucose of 15 cases was in the normal range, and the chloride of 19 cases was in the normal range. Among 16 cases with brain magnetic resonance imaging examination, eight cases did not show abnormality, six cases with local meningeal linear enhancement, one case with small intracranial malacia, and one case with extensive intracranial lesions. For 13 cases who received electroencephalogram (EEG) test, seven cases showed normal EEG or marginal state, four cases showed extensive medium and high amplitude slow wave, one case showed spike wave or spike slow wave and one case had both of the above two changes. Among 23 children, 22 cases recovered including one case had secondary epilepsy, and the remaining one case had severe brain dysfunction and was unable to suck when discharged, with an indwelling gastric tube and accompanied by secondary epilepsy. Conclusions:The clinical manifestations and auxiliary examinations of children with AE have no obvious specificity. Most children with AE have a good prognosis, but a small number of them may have serious sequelae.

OBJECTIVE: To explore the effects of taurolithocholic acid (tLCA) and chenodeoxycholic acid (CDCA) on the expression of aorexigenic neuropeptide in mouse hypothalamus GT1-7 cells. METHODS: Mouse hypothalamic GT1-7 cells were treated with culture medium containing 10% FBS (control group, =3) or with 10 nmol/L, 100 nmol/L, 1 μmol/L and 10 μmol/L tLCA (tLCA group, =3) or CDCA (CDCA group, =3) for 12, 24 or 48 h. Real-time PCR was performed to determine the expression levels of proopiomelanocortin (POMC) mRNA in the cells, and the production levels of α-melanocyte-stimulating hormone (α-MSH) were assessed using an ELISA kit. Signal transduction and activator of transcription 3 phosphorylation (p-STAT3), threonine kinase phosphorylation (p-AKT), suppressor of cytokine signaling 3 (SOCS3), G protein-coupled bile acid receptor-1 (TGR5) and farnesoid X receptor (FXR) protein were detected by Western blotting. RESULTS: Western blotting results showed that mouse hypothalamic GT1-7 cells expressed two bile acid receptors, TGR5 and FXR, whose expressions were regulated by bile acids. Real-time PCR showed that the expression of POMC mRNA was significantly increased in the cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. POMC-derived anorexigenic peptide α-MSH increased significantly in GT1-7 cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. Treatment of the cells with tLCA or CDCA significantly increased the expressions of intracellular signaling proteins including p-STAT3, p-AKT and SOCS3. CONCLUSIONS Mouse hypothalamic GT1-7 cells express bile acid receptors TGR5 and FXR. Bile acids tLCA or CDCA can promote the expression of POMC mRNA and increase the production of the anorexigenic peptide α-MSH. The intracellular signaling proteins p-AKT, p-STAT3 and SOCS3 are likely involved in bile acid-induced anorexigenic peptide production.
Animals ; Cell Line ; Chenodeoxycholic Acid ; pharmacology ; Gene Expression Regulation ; drug effects ; Hypothalamus ; cytology ; Mice ; Neuropeptides ; genetics ; metabolism ; Pro-Opiomelanocortin ; genetics ; RNA, Messenger ; genetics ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Suppressor of Cytokine Signaling 3 Protein ; metabolism ; Taurolithocholic Acid ; pharmacology ; alpha-MSH ; genetics

OBJECTIVE: To explore the effects of taurolithocholic acid (tLCA) and chenodeoxycholic acid (CDCA) on the expression of aorexigenic neuropeptide in mouse hypothalamus GT1-7 cells. METHODS: Mouse hypothalamic GT1-7 cells were treated with culture medium containing 10% FBS (control group, =3) or with 10 nmol/L, 100 nmol/L, 1 μmol/L and 10 μmol/L tLCA (tLCA group, =3) or CDCA (CDCA group, =3) for 12, 24 or 48 h. Real-time PCR was performed to determine the expression levels of proopiomelanocortin (POMC) mRNA in the cells, and the production levels of α-melanocyte-stimulating hormone (α-MSH) were assessed using an ELISA kit. Signal transduction and activator of transcription 3 phosphorylation (p-STAT3), threonine kinase phosphorylation (p-AKT), suppressor of cytokine signaling 3 (SOCS3), G protein-coupled bile acid receptor-1 (TGR5) and farnesoid X receptor (FXR) protein were detected by Western blotting. RESULTS: Western blotting results showed that mouse hypothalamic GT1-7 cells expressed two bile acid receptors, TGR5 and FXR, whose expressions were regulated by bile acids. Real-time PCR showed that the expression of POMC mRNA was significantly increased in the cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. POMC-derived anorexigenic peptide α-MSH increased significantly in GT1-7 cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. Treatment of the cells with tLCA or CDCA significantly increased the expressions of intracellular signaling proteins including p-STAT3, p-AKT and SOCS3. CONCLUSIONS Mouse hypothalamic GT1-7 cells express bile acid receptors TGR5 and FXR. Bile acids tLCA or CDCA can promote the expression of POMC mRNA and increase the production of the anorexigenic peptide α-MSH. The intracellular signaling proteins p-AKT, p-STAT3 and SOCS3 are likely involved in bile acid-induced anorexigenic peptide production.
Animals ; Bile Acids and Salts ; Chenodeoxycholic Acid ; Hypothalamus ; Mice ; Neuropeptides ; Phosphorylation ; STAT3 Transcription Factor ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein