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 explore the potential categories of post-traumatic stress disorder (PTSD) trajectories in women with multiple in vitro fertilization-embryo transfer (IVF-ET) failures, and to analyze the effects of different demographic characteristics and psychological factors on the potential categories of PTSD trajectories.Methods:This was a prospective empirical research, from May 2021 to October 2022, women with IVF-ET failure ≥ 2 times in the reproductive department of Shanghai First People′s Hospital from May 2021 to October 2022 were selected as the research objects. Post-traumatic stress disorder civilian version scale was used for 4 follow-ups at 3 d (T1), 10 d (T2), 20 d (T3) after the last transplantation failure and 3 d before the next transplantation cycle (T4). Telephone follow-up and online follow-up were combined to obtain the PTSD level at 4 time points. Potential categories of PTSD score trajectories at four time points were identified using a latent category growth model, and analyze influencing factors using unordered multi classification logistic analysis.Results:Totally 196 IVF-ET women were admitted, aged (29.42 ± 4.13) years. Three PTSD trajectories were fitted in this study, including 82 cases (42%) in non-PTSD group, 61 cases (31%) in mild PTSD group and 53 cases (27%) in elevated PTSD group. Logistic regression analysis showed that age, education level, fertility pressure and marital adjustment level were the predictors of PTSD trajectory in women with multiple IVF-ET failures. Compared with the non-PTSD group, women aged ≥35 years, with lower education level and marital adjustment level were more likely to enter the elevated PTSD group ( OR=4.570, 8.540, 0.949, all P<0.05). Women aged 35 years and with greater reproductive pressure were more likely to enter the mild PTSD group ( OR=3.871, 1.063, both P<0.05). Conclusions:There is group heterogeneity in the trajectories of PTSD in women with multiple IVF-ET failures in the next transplantation cycle. Old age, low education level, high fertility pressure and poor marital adjustment can predict the trajectories of PTSD. Fertility stress and marriage adjustment are changeable variables. Medical staff can relieve women′s fertility pressure through health education and mindfulness intervention, promote a good state of marriage adjustment, and minimize the adverse effects of PTSD on the next cycle of conception.

Objective To investigate the appropriate venous access for obese patients undergoing metabolic and bariatric surgery by comparing the clinical outcomes of different lengths of peripheral intravenous catheters.Methods Inpatients who underwent bariatric surgery in a tertiary hospital in Zhejiang from August 2022 to December 2022 were selected as the study population using a fixed-point continuous convenience sampling method.A stratified block randomisation method was used to divide the group into an experimental group 1(mini-midline catheters),an experimental group 2(midline catheters)and a control group(short peripheral intravenous catheters,Short PIVCs).The incidence of catheter-related complications,the rate of extubation due to complications,the duration of catheter retention,the time to first catheter-related complication were compared in the 3 groups.Results A total of 186 patients were included,with 62 patients in each group.The overall incidence of catheter-related complications in experimental group 1,experimental group 2,and control group were 25.81％,8.06％,and 58.06％.The extubation rates due to complications were 19.35％,4.84％,and 41.94％,and the duration of catheter retention was 7.00(6.00,7.00)d,7.00(6.00,7.00)d,6.00(3.00,6.25)d.The differences were statistically different(P＜0.05)when comparing the 3 groups.Among them,the differences in the overall incidence of catheter-related complications and the rate of extubation due to complications were statistically significant when comparing experimental group 1 with the control group,experimental group 2 with the control group,and experimental group 1 with experimental group 2(P＜0.017);the duration of catheter retention in both experimental group 1 and experimental group 2 were higher than it in the control group,and the differences were statistically different(P＜0.017).Conclusion The complication rate of mini-midline catheters and midline catheters is lower than that of short ones,and the indwelling time is consistent with the perioperative period of metabolic and bariatric surgery,which is suitable for use in patients undergoing metabolic and bariatric surgery.

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*

Objective:To explore the epidemiological characteristics, risk factors, preventions and treatments of recent human parvovirus B19 (HPV-B19) infections in recipients of renal transplantation (RT).Methods:From May 2020 to June 2021, retrospective review was conducted for epidemiological characteristics, treatment protocols, preventions and outcomes of HPV-B19 infected recipients after RT.Risk factors were analyzed using uninfected recipients after RT in the same period as controls.And 78 recipients who were not infected after RT with similar operation time were used as a control group for risk factor analysis.The infection rates of the four liver transplant recipients infected with HPV-B19 during the same period were calculated and compared with those of the kidney transplant recipients.Chi-square test and Fisher's exact test were used for statistical analysis.Results:During the observation period, HPV-B19 infection occurred in 39/368 recipients after RT with an overall infection rate of 10.60%(39/368). In terms of clinical symptoms, all 39 recipients presented with pure red cell aplasia (PRCA). In terms of season of infection, HPV-B19 infections occurred predominantly in autumn and winter [74.3% (29/39) of infections in autumn and winter, including 48.7% (19/39) in autumn]. Comparing the infection rates of different transplant recipients, 4 out of 123 liver transplant recipients were infected with HPV-B19 during the same period.The rate of infection was lower in liver transplant recipients than in RT counterparts (3.25% vs.10.60%, χ2=6.225, P=0.013). Analysis of OR values showed that transfusion of blood products was a risk factor for recent postoperative infection ( χ2=4.806, P=0.028, OR=2.418, 95% CI=1.088-5.373). Conclusions:HPV-B19 infection in renal transplant patients is mainly manifested as PRCA and is more likely than in liver transplant patients.Autumn and winter may be susceptible seasons for HPV-B19 and protection should be increased to prevent infection.Transfusion of blood products is a risk factor for recent HPV-B19 infection after RT, therefore donors should be routinely examined and it is imperative to test the safety of blood products in patients after RT.Thus HPV-B19 infection is well-controlled so that further spread may be prevented to avoid an epidemic outbreak.

Objective:To compare the efficacy of medial patellofemoral ligament (MPFL) reconstruction using single half tunnel, double half curved tunnel and suture anchor fixation in the treatment of patellar dislocation.Methods:A retrospective cohort study was used to analyze the clinical data of 58 patients with patellar dislocation treated in Second Hospital of Lanzhou University from June 2018 to February 2021, including 22 males and 36 females, aged 12-34 years [(19.6±5.5)years]. MPFL reconstruction was performed arthroscopically using single half tunnel fixation in 20 patients (single half tunnel group), double half curved tunnel fixation in 18 (double half curved tunnel group) and suture anchor fixation in 20 (suture anchor group). The Lysholm score, International Knee Documentation Committee (IKDC) score and Tegner activity score were compared among groups before operation, at 3 months after operation and at the last follow-up. The knee range of motion was compared among the three groups at 3 months after operation and at the last follow-up. The postoperative complications of the three groups were observed at the last follow-up.Results:All patients were followed up for 9-39 months [(26.5±9.1)months]. In single half tunnel group, double half curved tunnel group and suture anchor group, the Lysholm score was (78.4±12.0)points, (88.7±7.5)points and (81.1±9.8)points at 3 months after operation, and (80.4±14.2)points, (90.9±9.0)points and (83.3±9.1)points at the last follow-up. The postoperative Lysholm score in all groups was significantly increased from that preoperatively (all P<0.01). The Lysholm score in double half curved tunnel group was significantly higher than that in other two groups at 3 months after operation and at last follow-up (all P<0.05), but there was no significant difference between other groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the IKDC score was (76.7±12.2)points, (78.4±8.9)points and (81.0±8.1)points at 3 months after operation, and (77.6±15.8)points, (83.2±7.8)points and (82.4±12.4)points at the last follow-up. The postoperative IKDC score in all groups was significantly increased from that preoperatively (all P<0.01), but there was no significant difference among the three groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the Tegner score was (4.0±1.2)points, (5.4±1.7)points and (5.3±1.7)points at 3 months after operation, and (4.1±1.4)points, (5.8±1.8)points and (5.3±2.2)points at the last follow-up. The postoperative Tegner score in all groups was significantly improved from that preoperatively (all P<0.01). The Tegner score in single half tunnel group was significantly lower than that in other two groups at 3 months after operation and at last follow-up (all P<0.05), but there was no significant difference between other groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the knee range of motion was (122.3±6.4)°, (121.7±7.1)° and (123.3±5.7)° at the last follow-up, which were significantly increased from (117.3±8.0)°, (115.3±7.9)° and (116.8±8.3)° at 3 months after operation (all P<0.05), with no significant difference among the three groups (all P>0.05). The postoperative complication rate was 10.0% (2/20) in single half tunnel group, 5.6% (1/18) in double half curved tunnel group, and 25.0% (5/20) in suture anchor group ( P>0.05). Conclusions:For patellar dislocation, MPFL reconstruction using single half tunnel, double half curve tunnel and suture anchor fixation have achieved satisfactory improvement of knee range of motion, but knee functional recovery is much better after double half curved tunnel fixation.

Objective:To investigate the consistency and correlation of the respiratory synchronization tracking and fiducial marker respiratory synchronization tracking in the Cyberknife stereotactic body radiotherapy (SBRT) with the diaphragm as the tracking target.Methods:A total of 11 patients hospitalized at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2018 to November 2019 were enrolled, including 8 cases of lung cancer, 2 cases of liver cancer with lung metastasis and 1 case of colorectal cancer with lung metastasis. All enrolled cases used fiducial marker tracking plan (RT) and diaphragm contour tracking plan (DT), and then all received tumor visualization simulation tests. Bland-Altman method was used to make the consistency analysis of the offset in the visualization tests process of 2 tracking plans at each respiratory time point. The minimum tolerance distance, uncertainty and average standard deviation and maximum standard deviation in the optimal model state plans were compared between the both plans by using t test. Results:Compared with RT, the translational standard deviations of DT tracking were listed as follows: head-foot direction (0.4±2.9) mm, left-right direction (0.3±4.4) mm, anterior-posterior direction (-1.8±6.8) mm. The Bland-Altman method showed that the consistency between RT and DT was better in the head-foot and left-right directions, and worse in the anterior-posterior direction; the synchronization was only better in the head-foot direction, and worse in both the left-right and anterior-posterior directions. Results of the model quality comparison showed that the uncertainty of RT was higher than that of DT, and the difference was statistically significant [(23±6)% vs. (9±4)%, t=-5.24, P = 0.001], while the differences of the minimum tolerance distance, average standard deviation and maximum standard deviation were not statistically significant (all P>0.05). Conclusions:Patients who use respiratory synchronization Cyberknife SBRT with the diaphragm as the tracking target have better consistency and synchronization in the head-foot direction, but worse in the left-right and anterior-posterior directions. Under the corresponding marginal margin of the target area in the left-right direction, for tumors near the diaphragm that are not visible in the visual test, it is potentially feasible to use the diaphragm as a tracking target to implement respiratory synchronization SBRT. For larger motion amplitudes in the left-right and anterior-posterior directions, more caution is required.

Objective:To study the clinical value of left ventricle Tei index in evaluating hemodynamics after interventional therapy of patent ductus arteriosus (PDA).Methods:From May 2017 to May 2019, 50 children with PDA who underwent interventional therapy (PDA group) and 27 healthy children (healthy control group) in Anhui Provincial Children’s Hospital were selected. The left ventricle Tei index, plasma brain natriuretic peptides (BNP), left ventricular end-diastolic dimension (LVDD), left ventricular ejection fraction (LVEF) were compared between 2 groups.Results:The left ventricle Tei index was not correlated with heart rate and age in 2 groups ( P>0.05). The left ventricle Tei index before operation in PDA group was significantly lower than that in healthy control group: 0.20(0.16, 0.25) vs. 0.27(0.20, 0.30), and there was statistical difference ( P<0.05). In PDA group, the left ventricle Tei index immediately, 3 d, 1 month and 3 months after operation was significantly higher than before operation: 0.38(0.29, 0.47), 0.32(0.26, 0.40), 0.30(0.27, 0.35) and 0.32(0.26, 0.37) vs. 0.20(0.16, 0.25), and there was statistical difference ( P<0.05); the plasma BNP immediately after operation was significantly lower than before operation: 288 (126, 433) ng/L vs. 582 (303, 1 675) ng/L, and there was statistical difference ( P<0.05); the LVDD 3 months after operation was significantly lower than before operation: (3.03 ± 0.54) cm vs. (3.38 ± 0.51) cm, and there was statistical difference ( P<0.05); the LVEF immediately after operation was significantly lower than before operation: (54.24 ± 6.09)% vs. (59.45 ± 5.93)%, the LVEF 1 and 3 months after operation was significantly higher than that immediately after operation: (63.18 ± 4.71)% and (65.46 ± 4.78)% vs. (54.24 ± 6.09)%, and there were statistical differences ( P<0.05). The left ventricle Tei index before operation was negatively correlated with inner diameter of PDA and plasma BNP ( r = -0.362 and -0.388, P = 0.013 and 0.009), and there was no correlation between LVDD and LVEF ( r = -0.192 and -0.283, P = 0.229 and 0.053); the differences of Tei index before operation and immediately after operation (ΔTei) was positively correlated with inner diameter of PDA ( r = 0.325, P = 0.030), and there was no correlation with BNP, LVDD and LVEF ( r = 0.234, 0.283 and -0.039, P = 0.126, 0.076 and 0.798). Conclusions:The left ventricle Tei index can quickly and accurately assess the change of hemodynamics after interventional therapy of PDA.

Objective To establish the model of goat intervertebral disc degeneration （IDD） induced by controllable axial compressive stress and evaluate its imaging and pathological characteristics. Methods Twenty goats were randomly divided into 4 groups (control group, 4-week pressure group, 8-week pressure group, 12-week pressure group, n=5, 40 N pressure). Disc height index (DHI) was used to evaluate the change of intervertebral disc height by X-ray, Pfirrmann classification method was used to observe the degree of intervertebral disc degeneration by magnetic resonance imaging (MRI), and histopathological observation and evaluation for intervertebral disc were conducted by HE staining and immunohistochemistry. Results DHI in control group showed no significant changes with the extension of pressure time, while DHI in the experimental group gradually decreased. There was no significant change in Pfirrmann classification in control group. In experimental group, with the extension of time, the higher the degeneration aggravated with the Pfirrmann classification increasing. In experimental group, HE staining showed that the disc nucleus pulposus decreased in volume and nucleus pulposus cells, which were gradually replaced by fibrous tissues. Immunohistochemical staining showed that type I collagen in the nucleus pulposus gradually increased, type Ⅱ collagen gradually decreased, and intervertebral disc degeneration occurred. Conclusions A certain axial compressive stress can lead to degeneration of goat lumbar intervertebral disc, and the degree of degeneration is gradually increased with the extension of time.

Objective:To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis.Methods:Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test.Results:In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) vs. 0.04 (0-0.29) μg/L, Z=0.932, P>0.05) and CK-MB (20.6 (11.2-58.2) vs. 29.0 (16.7-47.0) U/L, Z=1.906, P>0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 vs. 4/6, Fisher=5.689, P=0.031). Conclusions:The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.