Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Objective:To evaluate the application effect of mini-clinical exercise assessment (Mini-CEX) in clinical teaching of pediatrics of Chinese medicine, further optimize Mini-CEX scale with characteristics of pediatrics of Chinese medicine, and improve teachers' understanding of its connotation.Methods:A total of 50 pediatric clinical practice undergraduates were randomly divided into Mini-CEX group and control group, 25 in each group, with a total of 4 weeks of practice. The application effect of Mini-CEX was evaluated by clinical comprehensive ability assessment, and the students' evaluation on the introduction of Mini-CEX in clinical teaching was understood through questionnaire survey on the recognition, advantages and existing problems of various contents of Mini-CEX. SPSS 17.0 was used for t test and chi-square test. Results:Total scores and sub-item scores of clinical comprehensive ability examination in Mini-CEX group were higher than those in control group ( P < 0.05), and the satisfaction with teaching in Mini-CEX group was significantly higher than that in control group ( P < 0.05). Through the questionnaire, it was found that the students had a high degree of recognition for the items in the improved Mini-CEX scale, and thought it was more suitable for the internship study and effect evaluation of pediatrics of Chinese medicine, especially in the aspects of clinical communication skills and humanistic care. Conclusion:Mini-CEX has many advantages, such as improving the clinical comprehensive ability of undergraduates, teaching effect, flexible teaching methods, objective evaluation methods and focusing on the cultivation of doctor-patient communication skills, which is worthy of clinical promotion.

Objective To evaluate the use of endoscopic papillary balloon dilation in treatment of choledocholithiasis associated with peripapillary duodenal diverticulum.Methods From January 2017 to July 2018,a retrospective study was conducted on 124 patients with choledocholithiasis associated with peripapillary duodenal diverticula at the Department of Hepatobiliary Surgery,Second Hospital of Hebei Medical University.These patients were divided into the small endoscopic sphincterotomy combined with balloon dilation group (sEST+EPBD,n =60) and the simple papillary balloon dilation group (EPBD n =64).The operation time,one-time success rate of stone removal,complication and hospitalization stay were compared between the two groups of patients.Results The hospitalization expenses of the EPBD group was significantly less than the sEST+EPBD group (P＜0.05).The operation time of the EPBD group was significantly shorten than the sEST+EPBD group (P＜0.05).There were no significant differences in the one-time success rate of stone removal,complication rates and hospitalization stay between the two groups (P＞0.05).Conclusions Compared with sEST+EPBD,treatment of choledocholithiasis in patients with peripapillary duodenal diverticula using simple balloon dilation shortened the operation time,did not increase the complication rates and hospitalization stay.The procedure was safe and effective,and resulted in almost the same one-time success rate of stone removal.

Objective To provide theoretical and experimental proof for selecting and implying Tourette's syndrome(TS) animal models, validities of four TS models induced by chemical factors were compared. Methods Four TS models,namely AMP model,APO model,DO1 model and IDPN model were built up by using different chemical modeling agents. Through detecting spontaneous movement, climbing time and monoamine transmitters levels in striatum, four TS animal models were compared and evaluated from three levels of validities-face, prediction,construct. Results Compared with control group, spontaneous movement times raised ( t = 4. 746, P =0. 000) and level of DOPAC ( (0.99 ± 0. 177 ) ng/mg) in striatum increased (P = 0.029 ), and level of NE in striatum decreased in AMP model group( (0.11 ± 0.033 )ng/mg, P = 0.012). Compared with control group, climbing time prolonged (P = 0. 004) and levels of DA ( ( 10. 19 ± 1.23 ) ng/mg), 5-HT ( ( 0. 54 ± 0.08 ) ng/mg) in striatum raised(P=0. 019, P=0. 002),at the same time ,levels of DOPAC( (0.63 ±0.11 )ng/mg),HVA ((0.45 ±0.04 ) ng/mg) in striatum reduced (P ＜ 0.01 ) in APO model group; Compared with control group, levels of DA ( ( 13.66 ± 1.55 ) ng/mg), DOPAC( (0.80 ±0. 11 ) ng/mg), HVA( ( 1.04 ± 0.14) ng/mg) grew downwards in striatum of DOI model mice(P=0.029,P=0.001, P= 0.004). Compared with control group, level of 5-HT in striatum increased in IDPN300 group ( (0.77 ± 0.09) ng/mg, P = 0.031 ). ConclusionFace validity of AMP model is temporal and that of IDPN model is steady and persistent. AMP model,APO model and DOI model possess predictive validity. AMP model,APO model,DOI model and IDPN model have potentiality of becoming construct validity model.

0.05). Compared with model group, levels of DA and DOPAC in striatum reduced in Xieqing group (P

Objective To observe the clinical efficacy and safety of 0.1% mometasone furoate cream in the topical treatment of eczematous dermatoses including neurodermatitis and eczema. Methods A randomized double-blind parallel controlled clinical trial was conducted. The home made mometasone furoate cream or imported Eloson cream was topically used in patients with such dermatoses once daily for 4 weeks, respectively. Symptom/sign scores were evaluated at the beginning of the treatment and at the 1st, 2nd, 3rd, 4th week after the initiation of the treatment. Results Two hundred and eighty-four patients were enrolled in the trial, including 143 patients with eczema and 141 patients with neurodermatitis. There are 142 patients each in test group and control group separately. All symptom/sign scores and total scores were significantly decreased 1, 2, 3, and 4 week after the treatment. No statistically significant difference was observed between the two groups. The cure rate and improvement rate in eczema patients were 78.87% and 97.18% in the test group; 84.51% and 92.96% in the control group; respectively. While the cure rate and improvement rate in neurodermatitis patients were 75.71% and 100% in the test group; 80.28% and 94.37% in the control group; respectively. The cure rate and improvement rate of total patients were 77.30% and 98.58% in the test group; 82.39% and 93.64% in the control group; respectively. No statistically significant difference in efficacy was observed between the two groups. There was no severe side effect in the two groups. One patient had mild contact dermatitis in the test group. Conclusions These results suggest that 0.1% mometasone furoate cream is an effective and safe drug in the treatment of neurodermatitis and eczema.