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 compare five time series models and predict the monthly incidence of bacillary dysentery in Qinghai Province in 2024,and provide reference for the prevention and control.Methods The epidemic charac-teristics of bacterial dysentery in Qinghai Province from 2014 to 2023 were analyzed.R4.3.1 software was used for establishing seasonal autoregressive integrated moving average(SARIMA)model,Holt-Winters triple exponential smoothing(Holt Winters)model,exponential smoothing(ETS)model,neural network autoregression(NNAR)model,and trigonometric seasonality,Box-Cox transformation,ARMA errors,trend and seasonal components(TBATS)model.Fitting effect of the models was analyzed and accuracy was compared.Results From 2014 to 2023,a total of 5 833 cases of bacterial dysentery were reported in Qinghai Province,without deaths,male to fe-male ratio being 1.23∶1.The highest incidence was reported in 2016(15.45 per 100 000 people),and the lowest in-cidence was reported in 2023(3.68 per 100 000 people).Incidence increased from 2014 to 2016,then decreased,showing an obvious overall downward trend.Case number in＜5 years age group was the highest,accounting for 29.76％of the total cases(n=1 736).Regarding population distribution,the top three were children in childcare institutions and scattered children(35.56％),farmers(24.65％),and students(12.62％).Except the additive Holt-Winters model,the predicted trends of the other four models were consistent with actuality.The ETS model had the best fitting effect,with a relatively balanced overall performance(training set:MAE=0.13,RMSE=0.21,MAPE=19.55％;testing set:MAE=0.11,RMSE=0.16,MAPE=28.66％).It is recommended to pre-dict the incidence of bacillary dysentery in Qinghai Province based on ETS model.Conclusion From 2014 to 2023,bacterial dysentery in Qinghai Province showed a downward trend,with the peak of the epidemic from June to Au-gust.Preschool and scattered children were high-risk groups.Among the five prediction models,ETS model has the best fitting effect,and can be used to predict the incidence of bacillary dysentery.

[Objective]From the perspective of the analogy and metaphorical thinking,to explore YE Tianshi's characteristics in syndrome differentiation,treatment and medication in his work Case Records as A Guide to Clinical Practice.[Methods]The connotations of analogical and metaphorical thinking are discussed based on Yi·Xici(The Book of Changes)and Huangdi Neijing(The Yellow Emperor's Inner Canon).By studying Case Records as A Guide to Clinical Practice,the study analyzes disease mechanisms by referring to Five Movements and Six Qi,establishes therapeutic principles and methods by referring to organs and body functions,and guides medication by considering the"form"and"properties"of herbs.The influence of constitution and seasons on diagnosis and treatment is also considered.By employing research methods such as literature review and case analysis,particular attention is given to how YE Tianshi utilized analogy and metaphorical thinking to guide medication and treatment during the diagnostic process.[Results]The philosophical connotation of the concept of the analogy and metaphorical thinking mainly refers to the relationship of imitation among things.In traditional Chinese medicine,it can be divided into three categories:classification based on imitation,analogy based on imitation and interpretation of the Tao based on imitation.YE Tianshi applied analogy and metaphorical thinking clinically by referring Qi in analyzing disease mechanisms,referring to organs and body functions when establishing treatment principles,and using the"form"and"properties"of herbs to guide medication.He also emphasized constitution-based syndrome differentiation and seasonal treatments,highlighting the influence of the"harmony between heaven and humans"on human health.[Conclusion]In-depth study of YE Tianshi's application of analogy and metaphorical thinking in syndrome differentiation,treatment and medication can help better understand and apply analogy and metaphorical thinking,guiding modern traditional Chinese medicine clinical practice.

Objective To compare five time series models and predict the monthly incidence of bacillary dysentery in Qinghai Province in 2024,and provide reference for the prevention and control.Methods The epidemic charac-teristics of bacterial dysentery in Qinghai Province from 2014 to 2023 were analyzed.R4.3.1 software was used for establishing seasonal autoregressive integrated moving average(SARIMA)model,Holt-Winters triple exponential smoothing(Holt Winters)model,exponential smoothing(ETS)model,neural network autoregression(NNAR)model,and trigonometric seasonality,Box-Cox transformation,ARMA errors,trend and seasonal components(TBATS)model.Fitting effect of the models was analyzed and accuracy was compared.Results From 2014 to 2023,a total of 5 833 cases of bacterial dysentery were reported in Qinghai Province,without deaths,male to fe-male ratio being 1.23∶1.The highest incidence was reported in 2016(15.45 per 100 000 people),and the lowest in-cidence was reported in 2023(3.68 per 100 000 people).Incidence increased from 2014 to 2016,then decreased,showing an obvious overall downward trend.Case number in＜5 years age group was the highest,accounting for 29.76％of the total cases(n=1 736).Regarding population distribution,the top three were children in childcare institutions and scattered children(35.56％),farmers(24.65％),and students(12.62％).Except the additive Holt-Winters model,the predicted trends of the other four models were consistent with actuality.The ETS model had the best fitting effect,with a relatively balanced overall performance(training set:MAE=0.13,RMSE=0.21,MAPE=19.55％;testing set:MAE=0.11,RMSE=0.16,MAPE=28.66％).It is recommended to pre-dict the incidence of bacillary dysentery in Qinghai Province based on ETS model.Conclusion From 2014 to 2023,bacterial dysentery in Qinghai Province showed a downward trend,with the peak of the epidemic from June to Au-gust.Preschool and scattered children were high-risk groups.Among the five prediction models,ETS model has the best fitting effect,and can be used to predict the incidence of bacillary dysentery.

[Objective]From the perspective of the analogy and metaphorical thinking,to explore YE Tianshi's characteristics in syndrome differentiation,treatment and medication in his work Case Records as A Guide to Clinical Practice.[Methods]The connotations of analogical and metaphorical thinking are discussed based on Yi·Xici(The Book of Changes)and Huangdi Neijing(The Yellow Emperor's Inner Canon).By studying Case Records as A Guide to Clinical Practice,the study analyzes disease mechanisms by referring to Five Movements and Six Qi,establishes therapeutic principles and methods by referring to organs and body functions,and guides medication by considering the"form"and"properties"of herbs.The influence of constitution and seasons on diagnosis and treatment is also considered.By employing research methods such as literature review and case analysis,particular attention is given to how YE Tianshi utilized analogy and metaphorical thinking to guide medication and treatment during the diagnostic process.[Results]The philosophical connotation of the concept of the analogy and metaphorical thinking mainly refers to the relationship of imitation among things.In traditional Chinese medicine,it can be divided into three categories:classification based on imitation,analogy based on imitation and interpretation of the Tao based on imitation.YE Tianshi applied analogy and metaphorical thinking clinically by referring Qi in analyzing disease mechanisms,referring to organs and body functions when establishing treatment principles,and using the"form"and"properties"of herbs to guide medication.He also emphasized constitution-based syndrome differentiation and seasonal treatments,highlighting the influence of the"harmony between heaven and humans"on human health.[Conclusion]In-depth study of YE Tianshi's application of analogy and metaphorical thinking in syndrome differentiation,treatment and medication can help better understand and apply analogy and metaphorical thinking,guiding modern traditional Chinese medicine clinical practice.

OBJECTIVE: To explore the design points of a three-dimensional (3D) printed customized cementless intercalary endoprosthesis with an intra-neck curved stem and to evaluate the key points and mid-term effectiveness of its application in the reconstruction of ultrashort bone segments in the proximal femur. METHODS: Between October 2015 and January 2021, 17 patients underwent reconstruction with a 3D printed-customized cementless intercalary endoprosthesis with an intra-neck curved stem. There were 11 males and 6 females, the age ranged from 10 to 76 years, with an average of 30.1 years. There were 9 cases of osteosarcoma, 4 cases of Ewing sarcoma, 2 cases of chondrosarcoma, 1 case of liposarcoma, and 1 case of myofibroblastoma. The disease duration was 5-14 months, with an average of 9.5 months. Enneking staging included 16 cases of stage ⅡB and 1 case of stage ⅢB. The distances from the center of the femoral head to the body midline and the acetabular apex were measured preoperatively on X-ray images. Additionally, the distances from the tip of the intra-neck curved stem to the body midline and the acetabular apex were measured at immediate postoperatively and last follow-up. The neck-shaft angle was also measured preoperatively, at immediate postoperatively, and at last follow-up. The status of osseointegration at the bone-prosthesis interface and bone growth into the prosthesis surface were assessed by X-ray films, CT, and Tomosynthesis-Shimadzu metal artefact reduction technology (T-SMART). The survival status of the patients, presence of local recurrence or distant metastasis, and occurrence of postoperative complications were assessed. The recovery of lower limb function was evaluated pre- and post-operatively using the Musculoskeletal Tumor Society (MSTS) scoring system, and pain relief was evaluated using the visual analogue scale (VAS) scores. RESULTS: The patient's femoral resection length was (163.1±57.5) mm, the remaining proximal femoral length was (69.6±9.3) mm, and the percentage of femoral resection length/total femoral length was 38.7%±14.6%. All 17 patients were followed up 25-86 months with an average of 58.1 months. During the follow-up, 1 patient died of lung metastasis at 46 months postoperatively, and the remaining 16 patients survived tumor-free. There was no complication such as periprosthetic infection, delayed incision healing, aseptic loosening, prosthesis fracture, or periprosthetic fracture. No evidence of micromotion or wear around the implanted stem of the prosthesis was detected in X-ray and T-SMART evaluations. There was no significant radiolucent lines, and radiographic evidence of bone ingrowth into the bone-prosthesis interface was observed in all stems. There was no significant difference in the distance from the tip of the curved stem to the body midline and the apex of the acetabulum at immediate postoperatively and last follow-up compared with the distance from the center of the femoral head to the body midline and the apex of the acetabulum before operation, respectively (P>0.05), and there was no significant difference in the above indexes between immediate postoperatively and last follow-up (P>0.05). The differences in the neck-shaft angle at various time points before and after operation were also not significant (P>0.05). At last follow-up, the MSTS score was 26.1±1.2 and the VAS score was 0.1±0.5, which were significantly improved when compared with those before operation [19.4±2.1 and 5.7±1.0, respectively] (t=14.735, P<0.001; t=21.301, P<0.001). At last follow-up, none of the patients walked with the aid of crutches or other walkers. CONCLUSION The 3D printed customized cementless intercalary endoprosthesis with an intra-neck curved stem is an effective method for reconstructing ultrashort bone segments in the proximal femur following malignant tumor resection. The operation is reliable, the postoperative lower limb function is satisfactory, and the incidence of complications is low.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur/surgery* ; Lower Extremity ; Bone-Implant Interface ; Femur Head ; Artificial Limbs

Objective:To evaluate the safety and efficacy of a dedicated neonatal-infant brain 0.35 T MRI system.Methods:A dual-center controlled clinical trial was conducted with single-arm objective performance criteria. From June to July 2020, sixty-six infants aged 0-12 (6.3±3.4) months were recruited from Children′s Hospital of Soochow University and the First People′s Hospital of Lianyungang prospectively. All infants underwent brain MRI with a dedicated neonatal-infant 0.35 T brain MRI system, using the dedicated two-channel transceiver head coil. MRI protocol included spin echo T 1WI, fast spin echo T 2WI, fluid attenuated inversion recovery, diffusion weighted imaging and 3D gradient echo sequence. MRI sequences were set with three orientations (axial, sagittal and coronal). Each case received at least two scanning planes and two scanning sequences. Five-point Likert scoring system was used to evaluate the image quality of acquired images, and the target value was set as at least 3 points per image. The temperature, heart rate and breathe of the infants were recorded before and after MRI; the acoustic noise of the MRI system was measured during the scanning process; and the adverse reactions were recorded if presented. Results:Five infants successfully completed their examination during non-sedated sleep in a single attempt, and 61 infants after sedation with chloral hydrate. Based on MRI-based five-point Likert scoring system, 41 cases achieved a score of 5, 21 cases with a score of 4 and 4 cases with a score of 3. Cases with score of 3 was due to movement of the infants during the scan, which resulted in motion related artifacts. The vital signs of all infants showed stable before and after imaging, with heart rate of (126.8±12.9) beats per minute, breathe of (38.2±6.8) times per minute. It was found that 47 cases showed no sign of temperature raise after brain MRI, 15 cases had less than 0.3 ℃ raise and 4 cases had 0.3 ℃ to 0.5 ℃ raise. The noise recorded during the scanning process was (57.5±1.8) dB(A). One case had mild diarrhea on the day of MR scan, and the symptoms disappeared on the second day without treatment; no adverse reactions were found for the rest subjects.Conclusion:Dedicated neonatal-infant 0.35 T brain MRI system allows data acquisition with high safety and excellent image quality, which has potentials in the clinical applications.

Objective: To evaluate the accuracy and feasibility of coronary artery calcium score ( CACS) on virtual non-contrast scan ( VNC) images obtained from coronary artery CT angiography ( CCTA) scan with dual －layer spectral detector CT (SDCT) ． Methods : The data of 197 patients who underwent CCTA scan in hospital were analyzed retrospectively，and 88 patients with CACS ＞0 were further analyzed． Linear regression analysis of CACS and coronary artery calcium volume ( CACV) of true non-contrast (TNC) images and VNC images ( CACS-TNC， CACS-VNC，CACV-TNC，CACV-VNC) was performed to obtain linear regression equation and correction coefficients λ 1AVG and λ2AVG ．CACS-VNC and CACV-VNC were corrected by the corresponding regression equation and recorded as CCACS-VNC and CCACV-VNC，respectively．Spearman correlation coefficient was used for correlation analysis and Bland-Altman plot was used for consistency test．Mann-Whitney U test was used to compare the difference between the two groups. Results : For the total coronary artery，there was a strong correlation between CACS- TNC and CACS-VNC (rs = 0. 952，P ＜0. 001 ，λ 1AVG = 2. 19 ) ，CACV-TNC and CACV-VNC ( rs = 0. 954，P < 0. 001，λ2AVG = 1. 93) ．The results of Mann-Whitney U test showed that there was no significant difference between CACS-TNC and CCACS-VNC or between CACV-TNC and CCACV-VNC，and the Bland-Altman plot showed good consistency between CACS-TNC and CCACS-VNC ，CACV-TNC and CCACV-VNC． Conclusion VNC images based on SDCT can accurately measure CACS and be used for cardiovascular risk classification，which is expected to replace TNC scan and reduce the radiation dose of patients.

Objective:To study the effectiveness of a strategy for detecting early gastric cancer using high-definition gastroscopy.Methods:A total of 849 patients over 35 years old who underwent gastroscopy in the Seventh Medical Center of PLA General Hospital from December 2018 to January 2019 were enrolled to a prospective study. During gastroscopy, biopsies were taken at any suspicious lesions in patients who had never been infected with Helicobacter pylori. In ulcer-type lesions, biopsies were taken at the edge of the ulcer. Outside the atrophic area, biopsies were taken at lesions in the cardia which were reddish under white light, or lesions in the non-cardiac area which were white or showed clear borders under white light. Inside the atrophic area, biopsies were taken at elevated lesions with clear borders or irregular depressions on the top, or flat/depressed lesions with irregular borders or being ocherous under narrow band imaging. In addition, biopsies were performed on any lesion that did not meet the above standard but was considered necessary. The high-risk patients were followed up by gastroscopy to observe the detection and missed diagnosis of neoplasm that meet the above standard, and to determine the sensitivity and positive predictive value of the strategy. Results:A total of 548 patients were biopsied (781 lesions). Among the 327 lesions that met the above standard, 16 lesions (4.9%) were diagnosed as epithelial neoplasm, of which 10 (3.1%) were high-grade neoplasm. Among the 454 lesions that did not meet the standard, only 1 (0.2%) epithelial neoplasm was diagnosed, and there was no high-grade neoplasm. The positive predictive value of this screening strategy for gastric epithelial neoplasm and high-grade neoplasm was higher than those who did not meet the standard (4.9% VS 0.2%, χ2=19.49, P<0.01; 3.1% VS 0, P<0.001). There were 146 patients (17.2%, 146/849) followed up by gastroscopy. During the follow-up, 2 high-grade intramucosal neoplasms were found. 84.2% (16/19) of epithelial tumors and 83.3% (10/12) of high-grade neoplasm were detected during the initial gastroscopy. Conclusion:This screening strategy can efficiently detect early gastric cancer under high-definition gastroscopy.

To investigate the efficacy and safety of endoscopic bougie dilation and stent implantation for pediatric caustic esophageal stenosis. Clinical characteristics, diagnosis and treatment of children with pediatric caustic esophageal stenosis from October 2009 to December 2019 at Department of Gastroenterology, the Seventh Medical Center of PLA General Hospital were retrospectively analyzed. A total of 50 caustic esophageal stenosis cases were enrolled, among whom, 94.0% (47/50) received conservative treatment before sending to our hospital. Thirty-six (72.0%) of them accidently ingested caustic substance of alkali and 22.0% (11/50) of them accidently ingested caustic substance of acid. Forty-six children (92.0%) who ingested caustic agents were younger than 7 years old. The stenosis was more common in the upper esophagus, accounting for 64.0% (32/50). Twenty-seven cases (54.0%) underwent simple bougie dilation and 16 cases (32.0%) underwent bougie dilation combined with stent treatment. All 50 children underwent a total of 1 260 expansions. The numbers of simple dilations and dilations combined with stent implantation were 37.8±26.2, 20.9±12.6 respectively with significant difference ( t=2.453, P=0.021). Among them, 2 cases (4.0%) underwent surgery, 5 cases (10.0%) underwent surgery combined with dilatation and stent implantation. The stenosis diameter widened significantly after treatment (1.1±0.2 cm VS 0.2±0.1 cm, t=23.004, P<0.001), and the Stooler grade of dysphagia improved significantly (grade 3.5±0.5 VS 1.2±0.7, t=19.925, P<0.001). Perforation occurred in only 1 patient, who was cured by conservative treatment with stent implantation. The total effective rate was 100.0% (50/50) and the satisfaction rate was 98.0% (49/50). Endoscopic bougie dilation and bougie dilation combined with stent implantation is safe and effective for pediatric caustic esophageal stenosis. Combination with stent implantation can reduce the number of dilation times.