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 diagnostic value of digital mammography combined with serum glutathione specific gamma-glutamyl transpeptidase 1(CHAC1)and retinoic acid-induced protein 14(RAI14)in identifying benign and malignant breast masses.Methods:A total of 189 patients with breast masses who were treated at Handan Maternal and Child Health Care Hospital from June 2019 to June 2024 were prospectively selected as the research subjects.According to the results of pathological biopsy,they were divided into benign mass group(128 cases)and malignant mass group(61 cases).All patients underwent digital mammography detection.The levels of serum CHAC1 and RAI14 were detected by enzyme-linked immunosorbent assay(ELISA).The general clinical data of the patients were collected and analyzed.Multivariate logistic regression analysis was used to analyze the factors of influencing benign and malignant nature of breast masses.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of CHAC1 and RAI14 for the benign and malignant nature of breast masses.The Kappa test was used to assess the consistency of results between each diagnostic method and the pathological detection.Results:For 189 patients with breast masses,digital mammography identified 56 cases of malignant masses and 133 cases of benign masses,and 13 cases of them were misdiagnosis and 18 cases of them were missed diagnosis.It showed a moderate consistency with the results of pathological detection(Kappa=0.617,P<0.05).Compared with the benign mass group,the levels of serum CHAC1 and RAI14 in the malignant mass group were significantly higher,and the differences of them between the two groups were statistically significant(t=12.249,12.512,P<0.05).The age,menopausal time,CHAC1 and RAI14 of the patients were all risk factors that can affect the benign and malignant nature of breast masses(OR=1.368,1.305,1.897,1.995,P<0.05).The area under curve(AUC),sensitivity and specificity of CHAC1 were respectively 0.816(95%CI:0.753～0.868),70.49%and 89.06%in diagnosing the benign and malignant nature of breast masses.These indicators of RAI14 were respectively 0.838(95%CI:0.778～0.888),68.85%and 89.84%in diagnosing the benign and malignant nature.The combined detection of the three methods identified 74 cases of malignant masses and 115 cases of benign masses,with 15 cases of misdiagnosis and 2 cases of missed diagnosis,which showed an extremely high consistency with the results of pathological detection(Kappa=0.805,P<0.001).The sensitivity(96.72%),negative predictive value(98.26%)and accuracy(91.01%)of the combined detection of digital mammography,serum CHAC1 and RAI14 were significantly higher than those of each alone detection of them,and the differences of them were significant(x2=15.310,16.623,15.310,11.690,12.402,11.572,5.276,5.276,4.677,P<0.05).Conclusion:The levels of serum CHAC1 and RAI14 appear increase in malignant breast masses,and digital mammography combined with serum CHAC1 and RAI14 has a certain of identification value for benign and malignant nature of breast masses.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

Objective:To explore the diagnostic value of digital mammography combined with serum glutathione specific gamma-glutamyl transpeptidase 1(CHAC1)and retinoic acid-induced protein 14(RAI14)in identifying benign and malignant breast masses.Methods:A total of 189 patients with breast masses who were treated at Handan Maternal and Child Health Care Hospital from June 2019 to June 2024 were prospectively selected as the research subjects.According to the results of pathological biopsy,they were divided into benign mass group(128 cases)and malignant mass group(61 cases).All patients underwent digital mammography detection.The levels of serum CHAC1 and RAI14 were detected by enzyme-linked immunosorbent assay(ELISA).The general clinical data of the patients were collected and analyzed.Multivariate logistic regression analysis was used to analyze the factors of influencing benign and malignant nature of breast masses.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of CHAC1 and RAI14 for the benign and malignant nature of breast masses.The Kappa test was used to assess the consistency of results between each diagnostic method and the pathological detection.Results:For 189 patients with breast masses,digital mammography identified 56 cases of malignant masses and 133 cases of benign masses,and 13 cases of them were misdiagnosis and 18 cases of them were missed diagnosis.It showed a moderate consistency with the results of pathological detection(Kappa=0.617,P<0.05).Compared with the benign mass group,the levels of serum CHAC1 and RAI14 in the malignant mass group were significantly higher,and the differences of them between the two groups were statistically significant(t=12.249,12.512,P<0.05).The age,menopausal time,CHAC1 and RAI14 of the patients were all risk factors that can affect the benign and malignant nature of breast masses(OR=1.368,1.305,1.897,1.995,P<0.05).The area under curve(AUC),sensitivity and specificity of CHAC1 were respectively 0.816(95%CI:0.753～0.868),70.49%and 89.06%in diagnosing the benign and malignant nature of breast masses.These indicators of RAI14 were respectively 0.838(95%CI:0.778～0.888),68.85%and 89.84%in diagnosing the benign and malignant nature.The combined detection of the three methods identified 74 cases of malignant masses and 115 cases of benign masses,with 15 cases of misdiagnosis and 2 cases of missed diagnosis,which showed an extremely high consistency with the results of pathological detection(Kappa=0.805,P<0.001).The sensitivity(96.72%),negative predictive value(98.26%)and accuracy(91.01%)of the combined detection of digital mammography,serum CHAC1 and RAI14 were significantly higher than those of each alone detection of them,and the differences of them were significant(x2=15.310,16.623,15.310,11.690,12.402,11.572,5.276,5.276,4.677,P<0.05).Conclusion:The levels of serum CHAC1 and RAI14 appear increase in malignant breast masses,and digital mammography combined with serum CHAC1 and RAI14 has a certain of identification value for benign and malignant nature of breast masses.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective:To explore the clinical efficacy of double traction-assisted reduction internal fixation and open reduction internal fixation in treating tibial plateau fractures.Methods:Data of patients with tibial plateau fracture admitted to West China Hospital of Sichuan University from January 2016 to December 2021 were retrospectively analyzed, and patients were divided into two groups according to treatment method: double traction-closed reduction internal fixation group (referred to as double traction group) and open reduction internal fixation group (referred to as open group). The double traction group included 21 patients, with 15 male and 6 female patients, with a mean age of 56.14±9.24 years (range, 45-72 years). Schatzker classification of fractures: 1 type I, 2 type II, 2 type III, 5 type IV, 6 type V, and 5 type VI. The open group included 29 patients, with 20 male and 9 female patients, with a mean age of 58.97±4.84 years (range, 47-70 years). Schatzker classification of fractures: 2 type I, 4 type II, 8 type III, 4 type IV, 5 type V, and 6 type VI. The surgical time, incision length, intraoperative blood loss, length of hospital stays, fracture healing time, postoperative time to full weight bearing, Rasmussen score, Hospital for Special Surgery (HSS) knee score, and complications were compared between the two groups of patients.Results:Both groups were followed up for 24 to 36 months, with an average of 30 months. There were significant differences in the operation time (92.61±6.22 min vs. 47.92±9.53 min), incision length (4.54±0.56 cm vs. 6.26±0.51 cm), and intraoperative blood loss (47.05±9.72 ml vs. 156.82±4.62 ml) between the group treated with closed reduction and double traction and the group treated with open reduction, with statistical significance ( t=18.83, 10.78, 53.24, P<0.001). There were also significant differences in the hospitalization time (5.35±0.41 d vs. 5.84±0.78 d), fracture healing time (3.72±0.74 months vs. 4.22±0.42 months), and time to full weight-bearing after surgery (11.29±1.10 weeks vs. 15.07±1.96 weeks) between the two groups, with statistical significance ( t=2.30, P=0.026; t=3.38, P<0.001; t=7.96, P<0.001). The HSS score at 6 months after surgery in the group treated with closed reduction and double traction was 81.61±2.32 points, which was higher than the score in the group treated with open reduction (77.66±4.01 points), with statistical significance ( t=4.07, P<0.001); at 12 months after surgery, the Rasmussen score in the group treated with closed reduction and double traction was 16.71±1.00 points, which was higher than the score in the group treated with open reduction (13.79±1.42 points), with statistical significance ( t=8.05, P<0.001). There was no fracture malunion or compartment syndrome occurred in both groups. The incidence of complications was 5% (1/21) in the group treated with closed reduction and double traction, and 10% (3/29) in the group treated with open reduction, with statistical significance (χ 2=0.52, P=0.473). Conclusion:The advantages of double traction-assisted reduction and internal fixation for tibial plateau fractures include minimal trauma, minimal bleeding, early mobilization, and shorter fracture healing time. It is a safe and reliable treatment method.

Objective To evaluate the efficacy of Anzhong-Fuyuan decoction combined with western routine therapy in the treatment of helicobacter pyiori(H.pylori)-positive chronic atrophic gastritis (CAG).Methods A total of 110 H.pylori positive CAG patients who met the inclusion criteria were divided into two groups according to random number table method,55 in each group.The control group was treated with quadruple therapy.On the basis of the control group,the study group was treated with Anzhong-Fuyuan decoction.Both groups were treated continuously for 40 days.The serum level of pepsinogen Ⅰ (Pepsinogen Ⅰ,PG Ⅰ),pepsinogen Ⅱ (PG Ⅱ),gastrin (GAS),endothelin (ET),CRP,IL-6 and TNF-α were detected by ELISA.The eradication rate of H.pylori was measured by 14C urea breath test,and the clinical efficacy was evaluated.Results The total effective rate was 92.7％ (51/55) in the study group and 78.2％ (43/55) in the control group.There were significant differences between the two groups (x2=4.681,P=0.031).The eradication rate of H.pylori was 89.1％ (49/55) in the study group and 76.4％ (42/55) in the control group.There was significant difference between the two groups (x2=3.911,P=-0.048).After treatment,the level of serum PG Ⅰ (84.87 ± 13.95 g/L vs.78.05 ± 12.69 g/L,t=3.434) and PG Ⅰ/PG Ⅱ (6.71 ± 1.26 vs.5.86 ± 1.13,t=2.861) in the study group was significantly higher than those in the control group (P＜0.05),and PG Ⅱ (12.64 ± 1.94 g/L vs.13.31 ± 2.10 g/L,t=3.725) was significantly lower than those in the control group (P＜0.01).The serum level of gastrin (10.76 ± 3.06 mmol/L vs.8.11 ± 2.84 mmol/L,t=4.707) was higher than that of control group (P＜0.01),endothelin (56.64 ± 4.42 ng/L vs.60.42 ± 5.13 ng/L,t=4.140) was significantly lower than that of control group (P＜0.01).After treatment,the level of CRP,IL-6 and TNF-α in the study group was significantly lower than those in the control group (t=11.100,9.571 and 8.687,respectively,all Ps＜ 0.001).Conclusions The Anzhong-Fuyuan decoction combined with routine therapy can significantly enhance the gastric mucosal secretion ability of H.pylori positive CAG patients,increase the ratio of PG Ⅰ/PG Ⅱ,promote the repair and regeneration of gastric mucosa,reduce the level of inflammatory cytokines.

In order to search for new adefovir analogues as anti-HBV agents with enhanced antiviral activity and hepatotrophic property,adefovir bis L-amino acid ester was used as lead compound to produce ten adefovir mono L-(thio)amino acid ester, mono bile acid ester derivatives(6a-6j). The design based on bile acid prodrug strategy,which can improve drug oral bioavaliability and liver-targeted enrichment by using enterohepatic circula-tion of bile acid.Sub-structure combination method was adopted to introduce L-(thio)amino acid ester and bile acid ester fragments on the phosphonate functionality of adefovir. The structures of target compounds were confirmed by 1H NMR, 13C NMR,ESI-MS and ESI-HRMS.HepG 2.2.15 cell were used for in vitro anti-HBV activity assessment.Compound 6c with high antiviral activity(EC500.92μmol/L,SI 512.63)was further investi-gated for its tissue distribution in mice.The results showed that content of compound 6c in liver was higher than that of adefovir dipivoxil,and in contrast its content in kidney was lower than that in positive control at all time points(0.25-12 h).Compound 6c exhibits higher antiviral activity,selective index and higher liver distribution,making it a potential anti HBV agent for further investigation.

Objective To investigate the constitutive characteristics and the change trend of gynecologic malignant tumors in hospitalized patients in Guangxi Zhuang Autonomous Region over the recent 20 years.Methods Clinical data of 8009 in-patients who suffered from gynecologic malignant tumors in 23 hospitals from 1985 to 2004 in Guangxi Zhuang Autonomous Region were analyzed,with respect to the tumor types and change trend.Results(1)The leading 4 types of malignant tumors were cervical cancers, ovarian cancers,endometrial cancers,and malignant trophoblastic tumors according to the constitutive ratios of the tumors.The constitutive ratio of cervical cancer patients rose year by year,from 17.48% during the 1985-1989 period to 49.25% during the 2000-2004 period(P0.05).(2)The occurring age of cervical cancers became younger obviously,from≥60 years old dropped to