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 explore the clinical application of distal and proximal bilateral lateral pre-decompression in replant of digit degloving injury.Methods:From March 2012 to May 2021, 14 patients with 29 digits had replantation surgery of degloved soft tissue and severed digits in Section II, Department of Orthopaedics, Changzhou Medical District of 904th Hospital of PLA Joint Logistic Support Force. There were 2 types of injuries: degloving injury of soft tissue but with intact digital tip, and digital tip degloving injury with intact distal phalanx and nail bed. With the technique of distal and proximal bilateral lateral pre-decompression, pre-decompression incisions were made to the subdermal on both sides of the degloved skin over the proper palmar digital arteries. From where, the distal stump of the proper palmar digital arteries and nerves for anastomosis were found and had them anastomosed with the proximal proper palmar digital arteries and proper palmar digital nerves, then anastomosed digital pulp and digital dorsal veins (11 cases were direct anastomosis and 3 cases were bridged anastomosis). Follow-up was carried out by outpatient consultation, telephone and WeChat APP. The appearance of the digit body, the shape of digital pulp, the nails grow and the motions of the digits were observed, and the Evaluation Standard of Replantation of Severed Fingers by the Society of Hand surgery of Chinese Medical Association was used to evaluate the recovery of function.Results:All 29 segments of degloving digit survived. Small necrotic areas was found in 4 digits and healed after the change of dressing. The followed-up time was lasted for 3-36 months. There was no obvious atrophy found in all the digits. Appearances of digit pulp and nails were satisfactory with good sensational recovery for TPD at 6-10 mm, 7 mm in average. Motions of all the repaired digits were good. According to the Evaluation Standard of Replantation of Severed Fingers by the Society of Hand surgery of Chinese Medical Association, 23 digits were in excellent, 4 in good and 2 in poor, with a satisfactory rate at 93.1%.Conclusion:For a distal digit injury with intact distal soft tissue and relatively mild injury of blood vessels and nerves, using the method of distal and proximal bilateral lateral pre-decompression can help to achieve good appearance in survived digital pulp, good sensational recovery and good nail growth. An individualised treatment intra-and-after the surgery could offer an ideal therapeutic effect.

Objective To explore the roles of Th17 cells in paraquat-induced acute lung injury(ALI)in a murine models through investigating the expression of Th17 type cytokine IL-17 and the specific transcription factor of Th17 cells-RORγt mRNA. Methods Male Kunming mice were randomly divided into the normal control group and the poisoned group. The ALI model induced by PQ poisoning was produced by intraperitoneal injection PQ solu-tion (20 mg/kg),and the normal control group was given normal saline solution with the same volume. After treatment for 48 hours,the animals were sacrificed. H&E staining and TUNEL staining were done to measure histo-logical changes and apoptosis. Serum level of Th17 related-cytokines was assayed by ELISA. The mRNA ex-pression of RORγt and the protein expression of IL-17 in the lung tissue were detected by real time-PCR assay and western blot,respectively. Results Compared with the normal control group,the lung inflammation and apopto-sis were significantly higher in the poisoned group. The serum level of IL-17A was significantly increased (P <0.05) and the lung parenchyma RORγt mRNA and IL-17 protein levels were significantly increased. Conclu-sion IL-17 plays an important role in the pathogenesis of ALI induced by paraquat poisoning.

Objective To compare the position,volume and matching index (MI) of esophagus between quiet end-inspiration and end-expiration in three dimensional CT (3D-CT) assisted with active breathing control (ABC) and the corresponding phases in four dimensional CT (4D-CT).Methods Eleven patients with peripheral lung cancer underwent 4D-CT simulation scan and 3D-CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in succession.The 0％ phase was defined as end-inspiratory phase (CT0),while the 50％ phase was defined as end-expiratory phase (CT50).The proximal,mid-,and distal thoracic esophagus were delineated separately on CT0,CT50,CTEIH and CTEEH images.The position,volume and MI of each segment esophagus between CT0 and CTEIH,CT50 and CTEEH were compared.Results In the left-right (x) direction,the position differences in the proximal,mid-,and distal thoracic esophagus between CT0and CTEIH were (-0.02 ±0.16)cm,(0.06 ± 0.26)cm and (0.10 ± 0.33) cm respectively,and in the anterior-posterior (y) direction,the position differences were (0.04 ±0.24)cm,(0.04 ±0.12) cm and (0.08 ±0.15) cm respectively,and the position differences in the same direction were not statistically significant.In the x direction,the position differences of the proximal,mid-,or distal thoracic esophagus between CT50 and CTEEH were (-0.02 ±0.24) cm,(0.12 ± 0.37) cm and (0.26 ± 0.33) cm respectively,and in the y direction,the position differences were (0.03 ±0.21)cm,(0.04 ±0.17)cm and (0.14 ±0.18)cm respectively,and the position differences in x and y directions of proximal and mid-thoracic esophagus between CT50 and CTEEH were not statistically significant,while the position differences in x and y directions of distal thoracic esophagus between CT50and CTEEH were both statistically significant (t =0.025,0.024,P ＜ 0.05).The volumes of the proximal,mid-and distal thoracic esophagus were all larger in CT0and CT50 than those in CTEIHand CTEEH,but without statistical differences.The MIs of the volumes of the proximal,mid-and distal thoracic esophagus between CT0 and CTEIH were (0.50 ± 0.17),(0.50 ± 0.19) and (0.56 ± 0.08),respectively,and those between CT50and CTEEH were (0.50 ±0.16),(0.47 ±0.14) and (0.51 ±0.15),respectively.The MI of each segment esophagus between CT0and CTEIHwas larger than that between CT50 and CTEEH,but without statistical differences.Conclusions The influence of breathing modes on the centroid positions of the proximal,mid-thoracic normal esophagus were not significant and there were spatial mismatches for any segment esophagus between 3D-CT assisted with ABC and 4D-CT.

Objective To analyze artifacts of gross tumor volume (GTV) and correlated factors in each phase images of four dimensional CT (4DCT) for peripheral lung cancer based on three dimensional CT (3DCT) assisted with active breathing control.Methods Nineteen patients with peripheral lung cancer underwent 3DCT (CTFB) and 4DCT simulation scans during free breathing and then underwent 3DCT simulation scans in end inspiration hold (CTEIH) and end expiration hold (CTEEH) assisted with active breathing control.The relative deviations (Devref) between the reference GTV (GTVref) and the GTVsdelineated based on CTFB (GTVFB) and all phases of 4DCT were calculated respectively.Correlations between GTVref and Devmax and between the tumor motion in the cranio-caudal (CC) direction and Devref were analyzed.Results The maximum median Devref of GTV was GTVFB with 17.83％,and the maximum median Devref of the GTV in all phases of 4DCT was GTV30 with 17.20％.A significant negative correlation was found between GTVEIH and Devmax (r =-0.691,P =0.001).The Devref was crrnelated with the tumor motion amplitude in the CC direction (r =0.323-0.617,P =0.005-0.150).The partial regression coefficient of influence of GTVref size and motion amplitude in the CC direction to the tumor Devmax were -0.500 and 0.583,P =0.002 and 0.001,respectively.Conclusions The GTV artifacts in different phase of 4DCT for the peripheral lung cancer were different to each other,and the influence of target displacement to artifacts was larger than that of target volume,so artifacts could be reduced by controlling breathing to reduce target displacement.

Objective To investigate the modulatory effects of glycyrrhizin (GL) on the expressions of nu-clear factor kappa B (NF-κB), glucocorticoid receptor (GR) and cytokines in serum, and to explore the protective mechanism of GL in acute lung injury (ALI) induced by lipopolysaecharide (LPS). Method Twenty-four male Sprague-Dawley rats were randomly(random number) divided into three groups (n = 8 in each) : normal group, ALI group and GL treatment group. Rats in the ALI group and GL treatment group were administered with LPS (5 mg/kg) intravenously. In GL treatment group, rats were treated with GL (20 mg/kg) one hour before LPS injec-tion. The animals were sacrificed 4 hours after injection of LPS, and then the lung wewt/dry ratio and PaO_2 were measured, the histopathology of lung injury was observed under light microscope, the expressions of NF-κB mRNA and GR mRNA in lung tissues were detected by using RT-PCR, and the levels of NF-κB protein and GR protein were determined by using Western blot. The levels of TNF-α and IL-10 in serum were observed by using ELISA.Data were analyzed with SPSS version 13.0 software, and means were compared with analysis of variance and Stu-dent-Newman-Keuls test. Results (1) TNF-α levels in normal group, ALI group and GL treatment group were (43.96±7.57), (153.68±20.42), and (87.23±7.52) ng/L, respectively, and IL-10 levels were (24.72±8.03), (42.48±6.81) and (58.33±9.62) ng/L, respectively (F = 183.70, all P <0.01). (2) NF-κB mRNA expressions in normal group, ALI group and GL treatment group were (0.432±0.085), (3.414±0.521) and (1.894±0.272), respectively, and NF-κB protein levels were (45.6±7.3), (254.7±16.4)and (133.5 ±11.7) ng/L, respectively, and comparison between groups showed statistical significant (F = 187.82 and 1466.53, ALL P < 0.01). GR mRNA expressions in normal group, ALI group and GL treatment group were (0.434±0.013), (0.152±0.025) and (0.308±0.033), respectively, and GR protein levels were(54.6±6.5), (11.5±2.3)and (28.2±5.6) ng/L, respectively (F = 246.00 and 260.92, all P < 0.01). (3) Com-pared with normal group, infiltration of PMNs, capillary congestion and swelling were found in ALI group, and treatment with GL could attenuate the lung injury. Conclusions Glycyrrhizin has a protective effects on rats with ALI induced by LPS maybe through down-regulating the expressions of NF-κB mRNA and TNF-α mRNA, and up-regulating the expression of GR mRNA and level of IL-10 protein.

AIM: To observe the changes of iNOS and eNOS in lung tissue and NO in bronchoalveolar lavage fluid (BALF) in smoking rats. METHODS: 80 Wistar rats were divided into control, smoking group, L-NIL group and L-NAME group (rats were exposed to smoke and injected (i.p.) with selective iNOS inhibitor L-NIL or NOS inhibitor L-NAME). iNOS and eNOS protein levels in whole lung were detected by immunohistochemical staining, and NOS mRNA was quantified using RT-PCR. In addition, NO - 2/NO - 3 was determined using Griess assay. RESULTS: The expression of iNOS mRNA and protein in smoking rats increased, the expression of eNOS mRNA and eNOS protein decreased, and the total cell count and the level of NO - 2/NO - 3in BALF increased( P