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.

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To explore the targets and molecular mechanisms of salidroside in improving cognitive function at high altitudes using network pharmacology,molecular docking,and experimental validation.Methods The SwissTargetPrediction platform was used to screen for salidroside-related targets,and the GeneCards database was used to search for targets associated with high-altitude cognitive function.The VENNY 2.1 platform was used to create a Venn diagram showing the intersection of salidroside and the targets of high-altitude cognitive function.The STRING11.5 database was used to construct a protein-protein interaction network diagram to screen for the key targets.The DAVID database was used to perform the Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and a component-target-pathway network was constructed using the Cytoscape 3.7.2 software platform.Furthermore,molecular docking and experimental studies were conducted for preliminary validation.Male C57BL/6J mice were randomly assigned to three groups,a low-altitude control group(Con group)receiving sterile water via intragastric gavage,a high-altitude hypoxia group(Hyp group)receiving sterile water via intragastric gavage,and a salidroside group administered with 10 mg/kg salidroside via intragastric gavage.The Hyp group and the salidroside group were pre-treated for 3 days(once daily)before rapid ascension to an altitude of 4010 m.Then,the 2 groups were exposed to a hypoxic environment for 1 day and received an additional treatment.Hippocampal tissues were collected from all three groups,and the relevant proteins were measured by Western blot.Results A total of 100 salidroside targets,2212 high-altitude cognition-related gene targets,and 52 common targets were identified.The improvement in high-altitude cognitive function by salidroside could be closely associated with core targets such as VEGFA,GAPDH,MMP-9,HRAS,FGF-2,HSP90AA1,and MAPK1,involving mainly the PI3K-Akt,MAPK,and VEGF signaling pathways.According to the molecular docking results,GAPDH,MMP-9,and VEGFA showed the best binding ability with salidroside.Experimental findings showed that salidroside improved high-altitude cognitive function by regulating the levels of Bcl-2/Bax,SRC-1,NF-κB,Beclin-1,and LC3B Ⅱ/Ⅰ.Conclusion Salidroside exerts its therapeutic effects in improving high-altitude cognitive function by regulating the expression levels of proteins associated with cell apoptosis,cell proliferation,and cell autophagy,inhibiting inflammation and stress response,and reducing apoptosis and excessive autophagy in hippocampal neurons.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures.Methods Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively,and divided into open reduction and internal fixation group(posterior medial approach hollow anchor system fixation)and arthroscopic fixation group(Endobutton with loop plate fixation under arthroscopy).There were 20 patients in open reduction and internal fixation group,including 16 males and 4 females,aged from 26 to 74 years old with an average of(42.9±18.8)years old;13 patients on the left side and 7 patients on the right side;12 patients were classi-fied to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were grade Ⅱ and 6 patients were grade Ⅲ in back drawer test.There were 18 patients in arthroscopic fixation group,including 11 males and 7 fe-males;aged from 24 to 70 years old with an average of(53.5±13.4)years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classifica-tion;11 patients were grade Ⅱ and 7 patients were grade Ⅲ in back drawer test.Operation time,blood loss,and quality of im-mediate reduction were compared between two groups.Knee range of motion,knee back drawer test,and International Knee Documentation Committee(IKDC)grading,KT2000 stability evaluation and Lysholm function score of knee joint were com-pared at 6 months after operation.Results All patients were followed up for 8 to 16 months with an average of(12.3±1.9)months.There were no complications such as incision infection,fracture malunion or non-union,and internal fixation loosening occurred.The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation.Operation time and blood loss in open reduction and internal fixation group were(56.4±7.1)min and(63.2±10.2)ml,while(89.9±7.4)min and(27.7±8.7)ml in arthroscopic fixation group,respectively,and had significant difference between two groups(P＜0.05).There were no differences in immediate reduction quality(x2=0.257,P=0.612),knee joint range of motion at 6 months after opertaion(t=0.492,P=0.626),knee joint rear drawer test(x2=0.320,P=0.572),IKDC classification of knee joint(x2=0.127,P=0.938),KT2000stability evaluation(x2=0.070,P=0.791),and knee Lysholmfunction score(t=0.092,P=0.282)between two groups.Conclusion Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixa-tion for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results,and arthroscopic surgery has less bleeding,but also has a longer learning curve and longer operation time than traditional inci-sion surgery.The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.

The epidemiological and spatiotemporal distribution characteristics of human leptospirosis in Zhejiang Province from 2018 to 2022 were analyzed,to provide a scientific basis for formulating leptospirosis prevention and control strategies.Data on leptospirosis were collected from the China Information System for Disease Control and Prevention,and analyzed with descriptive epidemiological methods.ArcMap 10.8 software was used for spatial autocorrelation analysis and visual display of the results.SaTScan 10.1.2 software was used for spatiotemporal scanning,to analyze and describe the spatiotemporal aggrega-tion characteristics of leptospirosis.A total of 255 human cases of leptospirosis were reported in Zhejiang Province from 2018 to 2022,including one death;the average annual incidence was 0.084 3/100 000,and the average annual mortality was 0.000 3/100 000.The highest incidence of leptospirosis in Zhejiang occurred from August to October.Most cases were in middle-aged and older people 45-86 years of age(221 cases,86.67％).The number of cases was highest among people 65-69 years of age(57 cases).The male to female ratio was 4.67∶1.The main occupation was farming(190 cases,74.51％).The cumulative number of cases in Wenzhou and Lishui in 3 years(201 cases)accounted for 78.82％of the total cases.The global spatial auto-correlation analysis from 2018 to 2022 showed that the incidence of leptospirosis in the province presented a positive spatial au-tocorrelation.Local spatial autocorrelation analysis indicated that the"high-high"gathering areas were concentrated primarily in Wenzhou,Lishui,and Taizhou in the mountainous and hilly areas of southern Zhejiang Province.Spatiotemporal scanning anal-ysis revealed three clusters with high incidence in southern Zhejiang Province.The incidence of leptospirosis in Zhejiang Prov-ince showed clear regional clustering and seasonality,and the high incidence area was mainly in the mountainous and hilly areas of southern Zhejiang Province.The cases occurred mainly in middle-aged and older male farmers.Health education among rural resi-dents should be strengthened to prevent potential epidemic risks.

ObjectiveTo explore the influencing factors of different scores on predicting death risk of extremely low birth weight infants （ELBWI）. MethodsA total of 186 cases of ELBWI admitted by the Children's Hospital affiliated to Nanjing Medical University and the Lishui Branch of the Affiliated Zhongda Hospital of Southeast University were admitted from January 1， 2019 to January 1， 2021， and 125 ELBWIs were finally included after screening by inclusion and exclusion criteria. There were 47 cases in the death group and 78 cases in the survival group. General data and the items of score for neonatal acute physiology version Ⅱ （SNAP-Ⅱ）， simplified version of the score for neonatal acute physiology perinatal extension （SNAPPE-Ⅱ）， clinical risk index for babies （CRIB）， clinical risk index for babies Ⅱ （CRIB-Ⅱ） and the national critical illness score （NCIS） were collected. Univariate and multivariate analysis was performed and nomogram was evaluated using receiver operating characteristic curve （ROC）. ResultsIt was found that systolic blood pressure， maximum inhaled oxygen concentration， BE value and birth weight were important factors in ELBWI mortality risk assessment ［systolic blood pressure OR： 0.968， 95%CI： 0.938-0.999， P=0.043； maximum inhaled oxygen concentration OR： 1.020， 95%CI： 1.006-1.034， P=0.006； BE OR： 0.868， 95%CI： 0.786-0.959， P=0.005； birth weight OR： 0.994， 95%CI： 0.991-0.997， P=0.000］. ROC showed that the area under the curve of the above four variables is 0.71， and the 95% confidence interval is 0.610-0.799， which is better than CRIB score. ConclusionLower systolic blood pressure， higher inhaled oxygen concentration， higher BE and lower birthweight are important influencing factors to predict the death risk of ELBWI. The above four items should be included in the newly developed score assessment to obtain a more effective ELBWI prediction system.