Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Cross-Sectional Studies ; Urodynamics ; China

Bile acids (BAs) are produced in the liver and are the final product of cholesterol catabolism, with a wide range of biological effects. This article reviews the research advances in the synthesis, transport, and metabolism of BAs and the role of BAs in regulating hepatocytes and immunity via enterohepatic circulation, as well as the current research on traditional Chinese medicine in the regulation of BAs, in order to further understand the mechanism of action of BAs in affecting intestinal flora and liver function, expand the knowledge of its regulatory mechanism, explore the mechanism of action of traditional Chinese medicine and related pathways in regulating BAs, and provide new ideas for the prevention and treatment of liver-related systemic diseases by regulating BAs.

Objective:To construct a computed tomography (CT)-based three-dimensional digital model of small bowel, and investigate its application value for predication of small bowel length before bariatric surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 patients with obesity who were admitted to the Daping Hospital of Army Medical University from December 2018 to January 2019 were collected. There were 2 males and 1 female, aged from from 24 to 44 years, with a median age of 25 years. Patients underwent abdominal enhanced CT examination before operation, and the three-dimensional digital models of small bowel for each patient were constructed respectively. Of the 3 patients, 2 underwent sleeve gastrectomy and 1 underwent Roux-en-Y gastric bypass. The 3 patients were numbered as No.1, No.2, and No.3 according to the operation time. Observation indicators: (1) construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length; (2) intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length. Count data were represented as absolute numbers or percentages.Results:(1) Construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length: the three-dimensional digital models of small bowel for each patient were constructed respectively before operation. The volume of small bowel, area of each cross-section for the 10 cross-sections of small bowel, average area of cross-section of small bowel, preoperative prediction of small bowel length in the three-dimensional digital model of small bowel of No.1 patient were 1 312 985 mm 3, 174 mm 2, 154 mm 2, 143 mm 2, 172 mm 2, 345 mm 2, 213 mm 2, 357 mm 2, 173 mm 2, 382 mm 2, 154 mm 2, 227 mm 2, 578 cm. The above indicators of No.2 patient were 1 817 224 mm 3, 274 mm 2, 196 mm 2, 487 mm 2, 413 mm 2, 520 mm 2, 254 mm 2, 231 mm 2, 170 mm 2, 212 mm 2, 168 mm 2, 293 mm 2, 620 cm. The above indicators of No.3 patient were 2 183 019 mm 3, 320 mm 2, 408 mm 2, 281 mm 2, 222 mm 2, 194 mm 2, 219 mm 2, 188 mm 2, 419 mm 2, 326 mm 2, 235 mm 2, 281 mm 2, 777 cm. (2) Intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length: the length of small bowel measured intraoperatively for No.1, No.2, and No.3 patients were 570 cm, 600 cm, and 780 cm, respectively. The relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length of No.1, No.2, and No.3 patients were 1.40%、3.33%、0.38%, respectively. Conclusion:Three-dimensional digital model of the small bowel can predict the small bowel length before bariatric surgery.

Objective To investigate the timing of administration of Conbercept in the treatment of proliferative diabetic retinopathy (PDR) before operation and its effect on neovascularization vascular endothelial growth factor (VEGF).Methods 90 patients (90 eyes) with PDR who underwent vitrectomy (PPV) were randomly divided into groups A,B and C,with 30 cases in each group.Group A received no intravitreal injection of Conbercept before operation,group B received intravitreal injection of Conbercept 3 days before operation,and group C received intravitreal injection of Conbercept 5 days before operation.The operation condition,visual acuity level,concentration of vascular endothelial growth factor in aqueous humor and positive expression of vascular growth factor in neovascularization membrane were compared in the three groups.Results There was no significant difference in the incidence of iatrogenic hiatus during operation,transient high intraocular pressure and hyphema after operation in the three groups (P ＞ 0.05).Compared with group A,group B and C had shorter the operation time,less electrocoagulation,lower LogMAR BCVA (best corrected visual acuity) three months after operation (P ≤ 0.05).There was no significant difference in the concentration of vascular endothelial growth factor between group B and group C before vitreous injection (P ＞ 0.05).The expression of VEGF in aqueous humor of group B and group C was lower than that of group A (P ≤ 0.05),and the total positive expression rate of VEGF in neovascularization membrane of group B and group C was 76.67％ and 73.33％ respectively,lower than that of group A (100.0％,P ≤0.05).The vitreous re-bleeding of group B and group C was 6.67％ and 10.0％,lower than that of group A (32.14％,P ≤ 0.05).While there was no significant difference between group B and group C (P ＞0.05).Conclusions Vitreous injection of Conbercept before PPV in PDR patients can reduce the concentration of VEGF in aqueous humor and the positive expression rate of VEGF in neovascularization membrane,significantly improve visual acuity and reduce the incidence of postoperative complications.The effect of vitreous injection 3 and 5 days before PPV is basically the same.

Objective To investigate the role and potential mechanism of high mobility group box-1 protein (HMGB1) on improving the chemosensitivity of gemcitabine-resistant pancreatic cancer PANC1 ceils.Methods Gemcitabine-resistant pancreatic cancer PANC1 (PANC1-GR) cell line was established by using increased gradient concentration of gemcitabine.The si-HMGB1-PANC1 and si-HMGB1-PANC1-GR cells were established by the transfection with HMGB1 siRNA using liposome.The 50％ inhibitory concentration (IC50) and Resistance index (RI) of gemcitabine in 4 PANC1 cell lines with or without HMGB1 siRNA transfection were determined and calculated by CCK-8 assay.Western blot assay was used to detect the protein expression of HMGB1 in PANC1 and PANC1-GR cells and the expression of autophagy marker protein Beclin1 in the 4 PANC1 cell lines.Flow cytometry assay was used to evaluate the apoptosis rate of 4 pancreatic caner cell lines.Results The gemcitabine-resistant pancreatic cancer cell line PANC1-GR was successfully established,which could grow stably and passage in media with 100 μmol/L gemcitabine.The IC50 of gemcitabine in PANC1,PANC1-GR,si-HMGB1-PANC1,and si-HMGB1-PANC1-GR cells lines were (4.7 ±0.4) μmoL/L,(166.5 ± 13.6) μmol/L,(3.2 ± 0.3) μmol/L,and (52.4 ± 8.4) μmol/L,respectively.The IC50 in PANC1-GR wassignificantly higher than that in PANC1,while the IC50 in the transfected cells was significantly lower than that in untransfected cells,and the differences were both statistically significant (bothP ＜ 0.01).The RI value of gemcitabine in transfected and untransfected PANC1-GR cells was 35.4 and 16.4.The relative protein levels of HMGB1 in PANC1 and PANC1-GR were 0.17 ± 0.08 and 0.38 ± 0.11.The expression of HMGB1 in PANC1-GR was obviously higher than that in PANC1,and the difference was statistically significant (P＜0.01).The relative protein levels of Beclin1 in PANC1,PANC1-GR,si-HMGB1-PANC1 and siHMGB1-PANC1-GR cells were 2.68 ± 0.23,3.28 ± 0.15,0.68 ± 0.23 and 0.78 ± 0.11,which in two transfected cells was greatly lower than those in untransfected cells.The apoptosis level was (34.58± 3.14)％,(79.56±3.58)％,(19.41± 1.53)％,and (34.57±2.94)％.The apoptosis level in the 2 transfected cell lines were significantly higher than those in the 2 untransfected cell lines,and the differences were both statistically significant (P ＜ 0.01).Conclusions The inhibition of HMGB1 could improve the chemosensitivity of gemcitabine in pancreatic cancer PANC1 cells,which might be mediated by the activation of autophagy.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Objective To compare set?up error and the positioning and error correction time between the infrared markers automatic positioning+ ExacTrac ( A) and the manual positioning+ cone?beam computed tomography ( CBCT) image?guided radiotherapy ( IGRT) ( B) in intensity?modulated radiotherapy ( IMRT) for lung cancer. Methods A total of 20 patients with lung cancer were randomly divided into Group A and Group B. In Group A, after automatic positioning, a group of orthogonal X?rays images were taken using kV X?rays, which matched digitally reconstructed radiographs to obtain errors before correction. In group B, after manual positioning, images were taken using CBCT, which matched reference computed tomography images to obtain errors before correction. The positioning and error correction time was recorded in both groups. After error correction, errors after correction were obtained in each group using IGRT. Between?group comparison was made using the paired t test. Results The errors in lateral, longitudinal, vertical, and spinning vertical directions were significantly reduced after correction in both Group A and B (A:1.8±1?3 vs. 0.4±0?1, P=0?000;2.7±1?9 vs. 0.5±0?1, P=0?000;2.8±1?7 vs. 0.4±0?1, P=0?000;1.6±1?0 vs. 0.3±0?9, P=0?000;B:2.6±1?9 vs. 0.5±0?5, P=0?000;3.1±2?5 vs. 0.6±0?6, P=0?000;2.1±1?8 vs. 0.5±0?5, P=0?000;0.9±0?7 vs. 0.3±0?1, P=0?000). There were no significant differences in errors after correction between Group A and Group B (0.4±0?1 vs. 0.5±0?5, P=0?204;0.5±0?1 vs. 0.6± 0?6, P=0?257;0.4± 0?1 vs. 0.5± 0?5, P=0?518;0.3± 0?9 vs. 0.3± 0?1, P=0?755 ) . However, the positioning and error correction time in Group A was significantly shorter than that in Group B (199.1±16?2 vs. 315.2±13?7, P=0?000). Conclusions The application of ExacTrac or CBCT IGRT can substantially reduce set?up errors and improve set?up accuracy in IMRT. In addition, the application of the ExacTrac system can substantially shorten the positioning and error correction time.

The paper conducts a case study of Yangzhou No.1 People′s Hospital, introduces the practice of outpatient process opti-mization based on informatization support platform, analyzes the operation status of self-service outpatient service platform and existing problems.Based on the M/M/s model in queuing theory, the queuing model of payment for outpatient service in the hospital is construc-ted, the characteristics of queuing payment problems for outpatient service are revealed, the relationship between the sharing rate of self-service terminals and the average length of the queue in service windows, the average waiting time of patients.

Objective To observe the effects and feasibility of using walking and breathing exercises to help patients with chronic obstructive pulmonary disease in the community.Methods A hundred and one communitydwelling patients with moderate to severe chronic obstructive pulmonary disease were randomized into an experimental group (51 cases) and a control group (50 cases).The control group was given conventional pharmacotherapy,while the experimental group was given quantified walking (i.e.walking for a pre-set number of steps daily) and breathing exercises (15 minutes,3 sessions daily) to do at home for 48 weeks in addition to the conventional pharmacotherapy,.Both groups were evaluated before and after the 48 weeks of treatment using the 6-minute walk test (6MWT),a clinical COPD questionnaire,Medical Research Council (MRC) dyspnea scoring,a general anxiety/depression questionnaire and a pulmonary function test.In addition,days of hospitalization and incidence of acute exacerbation were also recorded and compared between the 2 groups.Results Among the 101 cases,92 (91.1％) completed the study (45 in the experimental group,47 in the control group,a difference which was not statistically significant).After treatment,the average 6MWT distance in the experimental group was significantly increased and significantly greater than that in the control group.No statistically significant intra-group or inter-group differences were observed with regard to the pulmonary function test or the MRC dyspnea scores.Intra-group comparison and inter-group comparison of the clinical COPD questionnaire scores and anxiety/depression scores did,however,reveal statistically significant differences.There was no significant difference in the average number of acute attacks or in the length of hospital stays.Conclusions Quantified walking and breathing exercises are effective and feasible therapy for patients with chronic obstructive pulmonary disease in the community.