Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Objective:To explore the correlation between attempted suicide and childhood trauma as well as inflammatory cytokines levels in adolescents with depressive disorder.Methods:From January to December 2021, a total of 164 adolescents with depressive disorder were included and categorized into attempted suicide group ( n=108) and non-attempted suicide group ( n=56) according to whether they accompanied attempted suicide or not. The Chinese version of the suicide module of MINI 5.0, the childhood trauma questionnaire(CTQ), and the center for epidemiological studies depression scale (CES-D) were used to assess suicidal behavior, childhood trauma and depressive symptoms, while the plasma inflammatory cytokines levels were measured by electrochemiluminescence technology. The data were statistically analyzed by SPSS 23.0 software. Logistic regression was applied to analyze the independent influencing factors of attempted suicide and the predictive value of each independent risk factor for attempted suicide was assessed by receiver operating characteristic curve(ROC) curves. Results:The prevalence of attempted suicide was 65.9%(108/164) in adolescents with depressive disorder.The univariate analyses showed that the total CTQ score ((55.19±12.44), (45.50±12.11)) ( t=-4.771, P<0.001), CES-D total score ((40.75±10.26), (32.98±13.39)) ( t=-4.131, P<0.001), IL-6 level(1.87 (1.32, 2.69) pg/mL, 1.56 (1.05, 1.87) pg/mL)( Z=-3.102, P=0.002), IL-10 level (0.53 (0.38, 0.83) pg/mL, 0.47 (0.31, 0.69) pg/mL) ( Z=-2.100, P=0.036) and IL-17A level (2.20 (1.52, 3.65) pg/mL, 1.67 (1.25, 2.97) pg/mL) ( Z=-2.254, P=0.024) in plasma of patients in the attempted suicide group were significantly higher than those in non-attempted suicide group. Logistic stepwise regression analyses showed that CTQ total score, IL-6, IL-10, and IL-17A were risk factors for attempted suicide in adolescents with depressive disorder.The ROC showed that the total score of CTQ combined with IL-6 (AUC=0.782, 95% CI=0.709-0.855, P<0.001), the total score of CTQ combined with IL-10 (AUC=0.765, 95% CI=0.688-0.841, P<0.001), and the total score of CTQ combined with IL-17A (AUC=0.762, 95% CI=0.684-0.840, P<0.001) had a larger area under the curve, indicating better recognition and prediction ability for attempted suicide, with high sensitivity and specificity. Conclusion:The incidence of attempted suicide in adolescents with depressive disorder is high, and which is closely related to childhood trauma and the levels of inflammatory cytokines.

Neoadjuvant chemoradiotherapy is a part of the current standard treatment mode for locally advanced rectal cancer,which enables a certain proportion of patients to achieve complete tumor response,improving the surgical resection rate and anal retention rate,and then prolonging the disease-free survival period of patients.MRI is the preferred imaging examination to evaluate the efficacy of neoadjuvant therapy.With the development of functional MRI,quantitative parameters derived from different imaging principles can provide more biological information about tumors,improving the clinical application value of MRI.Multi-parameter MRI combining conventional MRI sequences and functional sequences can more comprehensively evaluate the efficacy of neoadjuvant therapy,which is conducive to developing individualized treatment plans for patients in clinical practice and realize precision medicine.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective:To compare the changes of biliary microbiota after enteral extended biliary stents (EEBS) implantation with that of conventional plastic stents in animal experiment, and to preliminarily investigate its possible mechanism in preventing stents occlusion.Methods:A total of 12 healthy Bama minipigs were randomly assigned to the conventional plastic stent group ( n=6) and the EEBS group ( n=6) using simple random method. The bile samples of all pigs were collected before stents implantation and 4 weeks after stents placement. The biliary microbiota composition and diversity before and after different stents implantation were analyzed by 16S rRNA gene sequencing and compared. Results:No complications including acute cholangitis, perforation, bleeding, or death occurred in 12 pigs. Eight days after stents implantation, stents were out of bile duct in all pigs under endoscopy, while the bile samples were collected again for analysis. The main composition of biliary microbiota at the phylum level were Proteobacteria, Firmicutes and Bacteroidota. Alpha-diversities revealed the Shannon ( P=0.004) and Simpson index ( P=0.008) significantly decreased in the conventional stent group after stents placement, and Bata diversity analysis also showed a significant difference in microbial composition (Anosim: R=0.514 8, P=0.011). There was no significant difference in Observed species index ( P=0.095), Chao1 index ( P=0.136), Shannon index ( P=0.353), Simpson index ( P=0.227) or Bata diversity (Anosim: R=0.059 3, P=0.187) in the EEBS group before and after stents placement. LEfSe algorithm indicated Bacteroides_ fragilis and Proteobacteria- Gammaproteobacteria- Enterobacterales- Enterobacteriaceae- scherichia_ Shigella- Escherichia_ coli significantly increased in the conventional stent group, and Desulfobacterota- Desulfovibrionia- Desulfovibrionales- Desulfovibrionaceae- Bilophila significantly increased in the EEBS group after stents placement. Conclusion:The biliary microbiota change slightly after EEBS implantation in the short-term, and EEBS may prevent duodenobiliary reflux by prolonging the reflux path.