Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objectiveto investigate the differential expression of intestinal flora and serum metabolites and potential biomarkers in patients with pre-diabetic sputum syndrome. MethodA total of 34 patients with pre-diabetic sputum syndrome were included as the phlegm syndrome group，and 37 healthy people were selected as the normal group. Serum and fecal samples of the two groups were collected，and liquid chromatography-mass spectrometry （LC-MS） non-targeted metabolomics and 16S rRNA high-throughput sequencing technology were used to detect serum metabolites and different intestinal flora of the two groups and explore the relationship among pre-diabetic sputum syndrome，serum metabolites，and intestinal flora. ResultIn the distribution of disease syndrome elements in the phlegm syndrome group，the first five disease syndrome elements in terms of frequency and proportion were dampness （73.53%），Qi stagnation （58.82%），Yin deficiency （50.00%），blood stasis （41.18%），and heat （35.29%）. According to the frequency and proportion of disease location syndrome elements，the first three main disease location syndrome elements were spleen （100.00%），liver （41.18%），and kidney （23.53%）. The results of 16S rRNA high-throughput sequencing showed that there were 44 different intestinal flora between the two groups. In order genus，there were significant differences in Bifidobacterium，Veillonococcus，and Roseococcus between the two groups （P<0.05）. The diversity，abundance，and evenness of intestinal flora in the phlegm syndrome group were lower than those in the normal group，with the difference not statistically significant. There was no significant difference in the community structure between two groups. The results of serum metabolomics showed that there were 13 differential metabolites in the two groups，which were mainly concentrated in amino acid metabolism，bile secretion，bile acid biosynthesis，and lipid metabolism （P<0.05）. The correlation among differential metabolites，intestinal flora，and syndrome elements was analyzed，and the results showed that ① lysine was positively correlated with spleen，Yin deficiency，and blood stasis，while taurocholic acid was positively correlated with liver，kidney，blood stasis，and dampness，and there was a positive correlation between taurocholic acid and yin deficiency and heat. The taurochenodeoxycholic acid was positively correlated with liver and dampness，and there was a negative correlation between arachidonic acid and dampness，as well as a positive correlation between glucose and spleen and blood stasis. ② Clostridium was positively correlated with spleen，kidney，Yin deficiency，and Qi stagnation. Rosepiella was negatively correlated with spleen，and Sutterella was negatively correlated with dampness. Bacteroides was negatively correlated with the spleen and kidney，and Bifidobacterium was negatively correlated with the spleen and dampness. ③ Bifidobacterium was positively correlated with glycine，threonine，lysine，and deoxycholic acid significantly，negatively correlated with cholic acid significantly，and positively correlated with taurochenodeoxycholic acid and pyruvic acid. Clostridium was positively correlated with glycine significantly and positively correlated with threonine and lysine. Lachnospira was negatively correlated with glycine，threonine，and pyruvic acid. Lysine was also negatively correlated with Faecalibacterium and Eubacterium ventriosum and positively correlated with Megamonas. There was a positive correlation between taurocholic acid and glycine bile acid and Campylobacter，between taurochenodeoxycholic acid and Veillonococcus，and between glucose and Rosepiella and Eubacterium ventriosum. There was a negative correlation between pyruvic acid and Escheria-Shigella and between taurochenodeoxycholic acid and Prevotella. Conclusionthere are differences in intestinal flora and serum metabolites between patients with pre-diabetic sputum syndrome and healthy people. The intestinal flora and metabolites have been disturbed in the stage of pre-diabetes，Bifidobacterium，Clostridium，Lachnospira，glycine，threonine，and lysine may be the breakthrough to explore the development of pre-diabetic sputum syndrome.

Objective:To analyze the correlation between sagittal bearing movement and posterior tibial slope after Oxford unicompartmental knee arthroplasty (UKA) and its effect on clinical results.Methods:A total of 29 patients (30 knees) with anterior medial knee osteoarthritis who underwent Oxford third-generation UKA in the Department of Joint and Sports Medicine of the Second Hospital of Shanxi Medical University from January 2022 to March 2022 were retrospectively analyzed, including 7 males (8 knees) and 22 females (22 knees), aged 63.3±7.9 years (range, 47-84 years). The patients were divided into overhang group (9 knees) and non-overhang group (21 knees) according to whether there was overhang of the bearing in the sagittal X-ray film at 135° flexion after operation. The preoperative and postoperative Oxford Knee Score (OKS), tibial posterior slope angle and radiographic results of the bearing were compared between the two groups. Pearson correlation analysis was used to measure the relationship between postoperative sagittal bearing movement and OKS and tibial posterior slope.Results:All patients successfully completed the operation and were followed up for 7.2±1.1 months (range, 6-9 months). 30% (9/30) of the bearing were overhung. When the knee flexion was 135°, the position of the bearing in the overhang group was 83.33%±3.46%, and the posterior suspension distance was 1.12 ±1.80 mm, which was significantly higher than those in the non-overhang group (73.24%±3.40% and -4.45±2.37 mm, P<0.05). The bearing movement distance in the overhang group was 33.22%±8.51%, which was larger than that in the non-overhang group (23.36%±9.32%), and the difference was statistically significant ( P<0.05). The posterior tibial slope of the overhang group was 2.68°±2.20° at 6 months after operation, which was smaller than that of the non-overhang group (4.59°±2.69°), and the difference was statistically significant ( P<0.05). The OKS score was 19.00±8.84 in the overhang group and 19.14 ±7.00 in the non-overhang group at 6 months after operation, and the difference was not statistically significant ( P>0.05). Pearson correlation analysis showed that the overhang distance of the bearing was positively correlated with the bearing position at 135° knee flexion ( r=0.97, P<0.001), and negatively correlated with the posterior tibial slope ( r=-0.38, P=0.041). It was negatively correlated with the change of posterior tibial slope ( r=-0.37, P=0.045), positively correlated with the bearing movement distance ( r=0.68, P<0.001), and had no correlation with the position of the bearing at 0° knee flexion ( r=-0.15, P=0.423). The bearing movement distance was negatively correlated with the position of the bearing at 0° of knee flexion ( r=-0.82, P<0.001), positively correlated with the position of the bearing at 135° of knee flexion ( r=0.70, P<0.001), and negatively correlated with the posterior tibial slope ( r=-0.48, P=0.007). It was negatively correlated with the change of posterior tibial slope ( r=-0.39, P<0.001), and positively correlated with the overhang distance of bearing at 135° knee flexion ( r=0.68, P=0.033). Conclusion:The incidence of bearing overhang at Oxford UKA is 30%. The bearing overhang and the increase of the bearing movement distance are related to the decrease of the posterior tibial slope after the operation. Although no effect of bearing overhang on knee joint function was found, the posterior tibial slope should be adjusted during the operation to reduce the incidence of bearing overhang.

Objective To observe the value of artificial intelligence(AI)knowledge graph and image classification for quality control(QC)of chest posterior-anterior position X-ray radiograph(abbreviated as chest film).Methods Totally 9 236 chest films from 595 medical institutions in Anhui province imaging cloud platform were retrospectively enrolled.QC knowledge graph containing 21 classification labels were constructed.Firstly,QC of chest films based on the above knowledge graph were performed by 10 technicians for 2 rounds of single person and 1 round of multi person,and the results were recorded as A,B and C,respectively.Then AI algorithms were used to classify and evaluate based on knowledge graph,and the result was recorded as D.Finally,a QC expert reviewed results C and D to determine the final QC results and taken those as references to analyze the efficiency of the above 4 QC.Results The area under the curve(AUC)of AI algorithm for QC of chest films were all ≥0.780,with an average value of 0.939.The average precision of QC for chest films of A,B,C and D was 81.15％,85.47％,91.65％and 92.21％,respectively.Conclusion AI knowledge graph and image classification technology could be effectively used for QC of chest posterior-anterior position X-ray radiograph.

Purpose Develop deep learning models to assess the clarity of chest X-ray images and validate the model's effectiveness by comparing it with the subjective evaluations of radiologists.Materials and Methods A retrospective collection of 9 135 chest X-ray images from 590 hospitals in Anhui Province,spanning from June 2015 to August 2022,was organized involving multiple radiologists who repeatedly evaluated the clarity of the images using a five-level scoring system.Individual assessments were designated as A and B,whereas the collective result of multiple assessments was designated as C.By constructing a deep learning model based on ResNet-50,image clarity evaluations of chest X-ray images were performed,we used the result C as the training and testing data for the model.The model's evaluation results were denoted as D.A radiology quality control expert conducted an audit assessment of the model's evaluation results and the multi-person assessments of physicians,serving as the reference standard for image clarity.Their assessment results were labeled as E.Statistical analysis,including Spearman's rank correlation coefficient,root mean square error(RMSE)and accuracy was employed to evaluate the effectiveness of the model.Results Compared with the reference standard E,D achieved an average accuracy of 0.85,exceeding the accuracy of C,which stood at 0.84.The ρ values for A,B,C,D and E were 0.58(0.54,0.62),0.59(0.55,0.63),0.74(0.71,0.77)and 0.80(0.78,0.82),respectively.The model exhibited the highest correlation with E.The ρ between A and B was 0.45(0.41,0.49),indicating a lower correlation between two individual subjective assessments of image clarity.The RMSE values for A,B,C,D and E were 0.99,0.94,0.72,and 0.71,respectively.The model's RMSE was lower than that of manual assessments.Conclusion This research model is capable of accurately assessing the clarity of chest X-ray images,and reducing the subjective interference of manual evaluation through deep learning methods,thereby providing an effective and objective evaluation tool for the assessment of clarity in clinical radiographic images.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective:To observe the expression levels of small ubiquitinated protein specific protease (SENP) 1 and small ubiquitin-related modifier protein (SUMO) 1 in patients with diffuse large B-cell lymphoma (DLBCL), and analyze the clinical value of evaluating prognosis.Methods:The clinical data of 66 patients with DLBCL (DLBCL group) in Inner Mongolia People′s Hospital from February 2017 to October 2020 were retrospectively analyzed, and 60 cases of healthy people in the same period were selected as the healthy control group. The expression levels of SENP1 and SUMO1 were detected by enzyme linked immunosorbent assay (ELISA). The correlation between the expression levels of SENP1, SUMO1 and clinical characteristics was analyzed. The independent risk factors affecting the prognosis were analyzed by Cox multivariate analysis.Results:The SENP1 in DLBCL group was significantly higher than that in healthy control group (50.39 ± 6.86 vs. 7.47 ± 1.32), the SUMO1 in DLBCL group was significantly lower than that in healthy control group (8.84 ± 2.13 vs. 31.49 ± 5.89), and there were statistical differences ( t = 47.640 and 29.210, P<0.01). There were statistical differences in SENP1 and SUMO1 among patients with different clinical stages ( P<0.01). The expression levels of SENP1 and SUMO1 were correlated with clinical stage and international prognostic index (IPI) ( P<0.05), and were not correlated with age, gender, disease site and clinical symptoms ( P>0.05). The 3-year survival rate in patients with high SENP1 expression (30 cases) was significantly lower than that in patients with low SENP1 expression (36 cases), the 3-year survival rate in patients with high SUMO1 expression (38 cases) was significantly higher than that in patients with low SUMO1 expression (28 cases), and there were statistical differences (26.67% vs. 75.00% and 73.68% vs. 39.29%, P<0.05). Cox multivariate regression analysis result showed that clinical stage, IPI, SENP1 and SUMO1 were independent risk factors affecting the prognosis in patients with DLBCL ( HR = 1.352, 1.487, 2.048 and 3.295; 95% CI 1.180 to 1.691, 1.187 to 1.602, 2.536 to 4.023 and 2.752 to 5.325; P<0.05 or <0.01). Conclusions:In patients with DLBCL, SENP1 is highly expressed and SUMO1 is lowly expressed. The expression levels of SENP1 and SUMO1 are closely related to clinical stage and IPI in patients with DLBCL, and they are independent risk factors of the prognosis.

OBJECTIVE： To establish a method for simultaneous determination of 27 kinds of heavy metals and trace elements in Halloysitum album from different origins. METHODS： The sample was dissolved by wet digestion. Using inductively coupled plasma mass spectrometry （ICP-MS）， carrier gas was argon and collision gas was helium； plasma gas flow rate was 15.0 L/min；   flow rate of carrier gas was 1.17 L/min and collision gas flow rate was 5.0 mL/min； atomizer was Barbinton， and sampling depth was 8.0 mm； atomizing chamber temperature was 2 ℃； radio frequency power was 1.3 kW； peristaltic pump revolutions was 30 r/min. In full quantitative analysis model， the number of test points was 3， the analysis time was 0.1 s， the repetition was 3 times， clustering analysis was conducted by using PASW Statistics 18.0 software. RESULTS： The linear range of 27 kinds of heavy metals and trace elements were 0-200 μg/L（r≥0.996 5）； the quantitative limit was 0.003 41-75.485 μg/L and the detection limit was      0.001 1-24.350 0 μg/L. RSDs of precision， stability and repeatability tests were all less than 7％； average recovery was 72.3％- 129.1％ （RSD was 0.9％-9.4％， n＝6）. The content of Al was 0.01-123 220.20 mg/kg， and Al was the element with the highest content. Li， Na， Mg， K， Ca， V， Mn， Fe， Co， Ni， Zn， Ga， Se， Rb， Sr， Ba and U were the principal components of trace elements and could be used as characteristic elements； 26 batches of Halloysitum Album samples could be grouped into 4 categories. CONCLUSIONS： The established method is simple， fast and highly sensitive， can improve the precision and accuracy of test results， and it is suitable for the determination of heavy metals and trace elements in Halloysitum album.