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.

Objective:To screen differential proteins in the serum of workers with rare earth samarium oxide pneumoconiosis, in order to provide new ideas for finding its early diagnostic biomarkers.Methods:In April 2019, three male workers diagnosed with samarium oxide pneumoconiosis at a rare earth factory in Baotou City, Inner Mongolia Autonomous Region were selected as the observation group, and three male workers who were not exposed to dust were selected as the control group. The serum was sequenced using the Label-free proteomic method to screen for differentially expressed proteins, followed by cluster of orthologous groups of proteins (COG) annotation, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The interaction gene library retrieval tool database and Cytoscape 3.9.1 software were used to draw protein-protein interaction networks. CytoHubba plugin was used to screen for differentially expressed proteins with high scores, and real-time fluorescence quantitative polymerase chain reaction (RT/q-PCR) was used to validate the proteomic sequencing results.Results:A total of 45 up-regulated differentially expressed proteins and 5 down-regulated differentially expressed proteins were screened out in the serum of workers with rare earth samarium oxide pneumoconiosis. In the COG functional classification, post-translational modifications, protein turnover, and chaperones were the most numerous. GO enrichment included 25 entries for biological processes such as complement activation (classical pathways), 15 entries for cellular components such as extracellular recombinants, and 10 entries for molecular functions such as protein binding. The pathways identified by KEGG enrichment analysis mainly included infectious diseases, immune system, signal transduction, and immune related diseases. The top 10 scoring proteins were haptoglobin, complement C1r subcomponent, complement C1s subcomponent, apolipoprotein C-Ⅲ, apolipoprotein A-Ⅱ, prothrombin, afamin, complement component C8 gamma chain, complement component C6, complement component C7. The RT/q-PCR validation results showed that the mRNA expression levels of haptoglobin, prothrombin and complement C1s subcomponent in the observation group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusion:Ten differentially expressed proteins in the serum of workers with rare earth samarium oxide pneumoconiosis are screened, which provides a good idea for the screening of biomarkers for early diagnosis of samarium oxide pneumoconiosis.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To screen differential proteins in the serum of workers with rare earth samarium oxide pneumoconiosis, in order to provide new ideas for finding its early diagnostic biomarkers.Methods:In April 2019, three male workers diagnosed with samarium oxide pneumoconiosis at a rare earth factory in Baotou City, Inner Mongolia Autonomous Region were selected as the observation group, and three male workers who were not exposed to dust were selected as the control group. The serum was sequenced using the Label-free proteomic method to screen for differentially expressed proteins, followed by cluster of orthologous groups of proteins (COG) annotation, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The interaction gene library retrieval tool database and Cytoscape 3.9.1 software were used to draw protein-protein interaction networks. CytoHubba plugin was used to screen for differentially expressed proteins with high scores, and real-time fluorescence quantitative polymerase chain reaction (RT/q-PCR) was used to validate the proteomic sequencing results.Results:A total of 45 up-regulated differentially expressed proteins and 5 down-regulated differentially expressed proteins were screened out in the serum of workers with rare earth samarium oxide pneumoconiosis. In the COG functional classification, post-translational modifications, protein turnover, and chaperones were the most numerous. GO enrichment included 25 entries for biological processes such as complement activation (classical pathways), 15 entries for cellular components such as extracellular recombinants, and 10 entries for molecular functions such as protein binding. The pathways identified by KEGG enrichment analysis mainly included infectious diseases, immune system, signal transduction, and immune related diseases. The top 10 scoring proteins were haptoglobin, complement C1r subcomponent, complement C1s subcomponent, apolipoprotein C-Ⅲ, apolipoprotein A-Ⅱ, prothrombin, afamin, complement component C8 gamma chain, complement component C6, complement component C7. The RT/q-PCR validation results showed that the mRNA expression levels of haptoglobin, prothrombin and complement C1s subcomponent in the observation group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusion:Ten differentially expressed proteins in the serum of workers with rare earth samarium oxide pneumoconiosis are screened, which provides a good idea for the screening of biomarkers for early diagnosis of samarium oxide pneumoconiosis.

Objective:To analyze the growth characteristics of different genotypes of Japanese encephalitis virus (JEV) in different cell lines, and to provide scientific basis for the selection of cell lines in the study of JEV.Methods:BHK-21, Vero, C6/36, PK-15, DF-1, N2a, SH-sy5y and MDCK cell lines were selected. The proliferation ability of genotype 1 (NX1889 strain), genotype 3 (P3 strain) and genotype 5 (XZ0934 strain) JEV in these cell lines was evaluated by plaque assay and RT-qPCR.Results:Significant cytopathogenic effects (CPE) were observed in BHK-21, Vero, C6/36, DF-1, N2a and PK-15 cell lines across all three JEV genotypes. However, no significant differences in CPE characteristics were observed within the same cell line. SH-sy5y and MDCK cell lines did not show significant CPE, but virus proliferation was detected in SH-sy5y cell line, while MDCK cell line were found to be insensitive to JEV. No significant difference was observed in the proliferation curves of G1, G3 and G5 JEV in BHK-21, Vero and SH-sy5y cell lines. In C6/36 and PK-15 cell lines, the titer of G1 JEV was higher than that of G3 and G5. In DF-1 cell line, G5 demonstrated a higher titer than the other two genotypes, whereas in N2a cell line, G5 showed a lower titer than the other two.Conclusions:There are differences in the proliferation of three different genotypes of JEV in different cell lines, which can provide reference for the study of JEV in different directions.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Objective Taking typical cases of Western medicine as an example,this paper explores the connection between Chinese and Western medicine on the understanding of tongue elephants.Methods After collecting the literature with tongue diagram attached to the clinical imaging column published in NEJM magazine,extracting the symptoms,signs and Western medicine disease information recorded in the literature,the tongue diagram was diagnosed from three aspects:tongue quality,tongue moss and sublingual meridians,and whether the symptoms and signs of tongue correspond to a certain diagnosis result,and the results were analyzed.Results A total of 48 articles were included,including 6 literature on abnormal tongue dynamics,which could correspond to abnormal tongue morphology in traditional Chinese medicine.Thirty-four cases of abnormal tongue shape were found.Among them,12 cases could be diagnosed with corresponding TCM tongue diagnosis,including 7 cases of abnormal tongue shape and 5 cases of abnormal coating.The remaining 22 cases were secondary changes in tongue structure.There were 8 articles on abnormal tongue color,including 1 abnormal tongue color,1 abnormal sublingual chord,and 6 abnormal lichen color.Conclusion Starting from the form and function,explore the connection between Chinese medicine and Western medicine in their understanding of tongue diagnosis,and promote the objectification and standardization of Chinese medicine tongue diagnosis.

Objective To explore the abnormal changes of resting state functional connectivity of pain networks in patients with cervical discogenic pain(CDP).Methods The resting-state functional magnetic resonance imaging(rs-fMRI)data of 40 patients with CDP and 40 age-and gender-matched healthy controls(HC)were collected.The seed of posterior insula(PI)was used to define the pain network,and seed-based whole-brain functional connectivity analyses were performed to explore the difference of functional connectivity between CDP patients and HC,the associations between functional connectivity and clinical measures were analyzed.Results The functional connectivity between bilateral PI and bilateral thalamus(THA)was increased,and the functional connectivity between left PI and middle cingulate cortex(MCC),left postcentral gyrus(PoCG)and MCC were decreased in CDP patients.Moreover,the func-tional connectivity between right PI and left THA was positively correlated with visual analogue scale(VAS),and the functional connectivity between left PoCG and MCC was negatively correlated with VAS.Conclusion Functional connectivity abnormalities exist in pain network resting state of CDP patients,which may provide an imaging basis for revealing the neuropathological mechanism of pain in CDP patients.

ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome. MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group， with 45 cases in each group. The control group was treated with polymyxin B， and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators ［white blood cell （WBC） count， procalcitonin （PCT）， neutrophil apolipoprotein （HNL）］， inflammatory factors ［interleukin-6 （IL-6）， serum chemokine ligand 2 （CXCL2）］， and T lymphocyte subpopulations （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/ CD8⁺ value）， acute physiological and chronic health Ⅱ （APACHE Ⅱ） score before and after treatment， as well as bacterial clearance rate and 28-day survival rate after treatment were observed. Result① The experiment was completed， and 81 cases were included， including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% （31/41） and 52.5% （21/40）， respectively， and the observation group was higher than the control group （χ²=4.7， P<0.05）. ③ The WBC count， PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment （P<0.05）. Except for the WBC count， the PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group were lower than those of the control group （P<0.05）. ④ The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were increased after treatment （P<0.05）， and CD8⁺ was decreased （P<0.05）. In the control group， only CD3⁺ value was increased （P<0.05）. The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were higher than those in the control group， and the value of CD8⁺ was lower than that in the control group （P<0.05）. ⑤ The 28-day survival rate in the observation group was higher than that in the control group （χ²=4.3， P<0.05）. ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria， control infection， reduce the level of inflammatory factors， regulate the immune state of the body， and improve the short-term prognosis.