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.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

With the emergence of unhealthy dietary structures in people’s life， metabolic associated fatty liver disease （MAFLD） has gradually become the most important chronic liver disease in China， and there is also a gradual increase in the cases of MAFLD-associated liver cancer. Adipose tissue not only has the function of energy storage， but also secretes adipokines that play an important role in the development and progression of MAFLD and its associated liver cancer. Studies on the mechanism of adipokines have provided important help for the prevention and treatment of MAFLD， and a large number of studies have shown that the abnormal secretion of adipokines is associated with MAFLD and plays an important regulatory role in the development and progression of liver cancer. Adipokines are not only regulated at the gene level， but they can also interact with genes through specific pathways to co-regulate pathophysiological processes such as inflammation， metabolism， immunity， and cell proliferation in MAFLD and its associated liver cancer. This article reviews the latest studies on the association of adipokines with MAFLD and its associated liver cancer， in order to provide new directions for further research on the pathogenesis of liver cancer.

Objective To investigate whether glaucocalyxin A can reduce inflammatory response in rats with trau-matic fracture.Methods The rats were randomly divided into control group,model group,low GLA(GLA-L),high GLA dose group(GLA-H)and GLA?H+YC?1(HIF?1α inhibitor)group.The level of TNF?α,IL?6,CTX?Ⅰ,CTX?Ⅱ,S?Ca,S?P,BGP and the activities of iNOS and ALP were detected by ELISA.The density and thickness of bone trabeculae were measured by computed tomography.Apoptosis of femur tissue was detected by TUNEL.The cartilage morphology was observed by saffranin O?fast green staining.Western blot was applied to de?tect the expression of HIF?1α,VEGF,CD31,BMP?2,and collagenⅠ proteins in femoral tissue.Results Compared with the control group,the cartilage morphology of rats in the model group was significantly damaged,the level of serum TNF?α,IL?6,CTX?Ⅰ,CTX?Ⅱ,iNOS activity and apoptosis rate of femur tissue were in?creased.Serum S?Ca,S?P,BGP levels,ALP activity,bone trabecular density and thickness,HIF?1α,VEGF,CD31,BMP?2,collagen Ⅰ protein expression levels in femur tissue were all decreased(P<0.05).The mor?phology of cartilage tissue in GLA?L and GLA?H groups was significantly improved,and the level of serum TNF?α,IL?6,CTX?Ⅰ,CTX?Ⅱ,iNOS activity and apoptosis rate of femur tissue were all significantly de?creased.Serum levels of S?Ca,S?P,BGP,ALP activity,bone trabecular density and thickness,HIF?1α,VEGF,CD31,BMP?2,collagen Ⅰ protein expression level in femur tissue were significantly increased(P<0.05).YC?1 was able to weaken the therapeutic effect of GLA on traumatic fracture rats(P<0.05).Conclusions GLA alleviates inflammation and cartilage damage in rats with traumatic fractures,promotes angio?genesis and improves femoral morphology,possibly by activating the HIF?1α/VEGF signaling pathway.

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent

OBJECTIVES: This study aimed to investigate the correlation between clinical symptoms and unilateral chewing habits in patients with temporomandibular disorder (TMD) accompanied by tinnitus. METHODS: A total of 285 patients diagnosed with TMD at the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital between December 2020 and May 2024 were included and divided into two groups: tinnitus group and non-tinnitus group. Analysis was conducted on the proportion of patients with unilateral chewing habits in both groups, the correlation between the side of tinnitus and the side of unilateral chewing, and the correlation of tinnitus with TMD clinical symptoms (joint clicking, joint pain, and limited mouth opening) and unilateral chewing habits. The correlation of the type of disc displacement with unilateral chewing and tinnitus was also examined. RESULTS: In the tinnitus group, the proportions of patients with and without unilateral chewing habits were 90.70% (39/43) and 9.30% (4/43), respectively. In the non-tinnitus group, the proportions of patients with and without unilateral chewing habits were 76.03% (184/242) and 23.97% (58/242), respectively. The proportion of patients with unilateral chewing habits in the tinnitus group was significantly higher than in the non-tinnitus group (χ²=4.613, P<0.05). Correlation analysis showed a positive correlation between tinnitus and unilateral chewing habits (P<0.05). In the left-sided tinnitus group, the proportion of left-sided unilateral chewers [54.55% (12/22)] was higher than that of right-sided unilateral chewers [45.45% (10/22)]. In the right-sided tinnitus group, the proportion of right-sided unilateral chewers [81.82% (9/11)] was higher than that of left-sided unilateral chewers [18.18% (2/11)]. The difference was statistically significant (χ²=7.282, P<0.05). A positive correlation was also found between the side of tinnitus and the side of unilateral chewing habits (P<0.05). The proportion of patients with pain was significantly higher in the tinnitus group than in the non-tinnitus group (P<0.05). No significant difference in the proportion of joint clicking or limited mouth opening and disc displacement (no disc displacement, unilateral disc displacement, bilateral disc displacement, reducible disc displacement, or irreducible disc displacement) was found between the tinnitus and non-tinnitus groups (P>0.05). CONCLUSIONS TMD with unilateral chewing habits may be a contributing factor to unexplained tinnitus. Unexplained tinnitus is correlated with joint pain in patients with TMD.
Humans ; Tinnitus/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Mastication ; Male ; Adult ; Female ; Middle Aged ; Habits

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

Objective To compare the segmenting efficacy of automatic segmentation models for advanced gastric cancer(AGC)on CT virtual monoenergetic images(VMI),non-linear blending images(NLBI)and mixed-energy images(MEI)based on 3D-nnU-Net.Methods Totally 216 cases of AGC were retrospectively enrolled,among them 185 cases were used to construct,train and validate models and divided into training set(n=154)and test set(n=31)at the ratio of 5∶1,while the other 31 cases were used as validation set to evaluate the generalization of the models.The 70 keV energy level VMI(VMI70 keV),NLBI and MEI were reconstructed with whole-abdominal dual-energy mode venous CT,and automatic segmentation models of AGC,including VMI70 keV,NLBI and MEI models were constructed using 3D-nnU-Net,respectively.Taken manually segmented results as golden standards,the efficacy of each model for segmenting all lesions and T2 stage lesions in test set and validation set were evaluated using Dice similarity coefficient(DSC),intersection over union(IoU)and average symmetric surface distance(ASSD).Results For all lesions in test and validation sets,DSC of 3 models were all＞0.80.DSC and IoU of VMI70 keV and NLBI models were both higher,while their ASSD was lower than those of MEI model(all P＜0.05).For T2 stage AGC in both test set and validation set(each n=5),DSC of MEI model was lower than that of VMI70 keV and NLBI models(both P＜0.05),while IoU of MEI model was lower than that of VMI70 keV model(P＜0.05),and its ASSD was higher than that of NLBI model(P＜0.05).Conclusion All 3D-nnU-Net-based VMI70 keV,NLBI and MEI models could effectively segment AGC on dual-energy CT images,and the segmentation efficacy of the former two were better.