Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

BACKGROUND:Pravastatin is a clinically effective drug for the treatment of hypercholesterolemia and is now found to play a beneficial role in the treatment of CNS injury;however,the mechanism remains unknown. OBJECTIVE:To ascertain the possible mechanism of action and whether pravastatin medication can expedite functional recovery following sciatic nerve crush injury. METHODS:Male Sprague-Dawley rats were randomly assigned into:pravastatin(sciatic nerve crush injury+pravastatin gavage),negative control(sciatic nerve crush injury+saline gavage),and sham operation(sciatic nerve exposure but no injury+saline gavage).While the other two groups received comparable amounts of saline gavage,the pravastatin group received postoperative pravastatin(5 mg/kg)by gavage for 1 week.The general conditions of the rats in each group were observed after operation.Sciatic function index was evaluated at the end of the 2nd,4th,6th,and 8th week after operation,and the wet mass ratio of the gastrocnemius muscle was measured at the end of the 8th week after operation.The levels of inflammatory cytokines in serum were measured using ELISA.Histomorphometrics was used to measure the number of myelinated nerve fibers,fiber diameter,axon diameter,and myelin sheath thickness.RT-qPCR assay was used to measure the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor,and western blot was used to measure the protein expression of growth-associated protein 43. RESULTS AND CONCLUSION:Compared with the negative control group,the sciatic function index in the pravastatin group recovered faster(P<0.05)and was closer to the level of the sham operation group,the expression of tumor necrosis factor α and interleukin 6 in serum was lower(P<0.05)and close to that of the sham operation group,and the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor in the sciatic nerve increased(P<0.05 or P<0.01),the relative protein expression of growth-associated protein 43 in the sciatic nerve was also significantly increased(P<0.05),the number of myelinated nerve fibers was increased more,and the values of fiber diameter,axon diameter,and myelin sheath thickness were larger(P<0.01)and closer to those of the sham operation group.To conclude,treatment with pravastatin accelerates functional recovery from sciatic nerve crush injury by a possible mechanism of inhibiting the expression of tumor necrosis factor α and interleukin 6 and promoting the secretion of neurotrophic factors nerve growth factor and brain-derived neurotrophic factor.

Since 2020, with the Sino-foreign cooperative education of clinical medicine as the pilot project, Chongqing Medical University (CQMU) has integrated its high-quality resources with those from University of Leicester (UoL) and explored the practice of enhanced virtual blended learning model from the aspects of self-learning before class, practical application during class, and consolidation and improvement after class. In addition, the implementation of this model was ensured from the aspects of teacher-student communication, platform construction, and optimization of evaluation mechanism, so as to replace the traditional teaching model and promote the implementation of local internationalization strategy. At present, preliminary results of student training have been achieved, and the project has passed the clinical medicine professional certification of the Ministry of Education and CQMU-UoL interim review.

Objective:To investigate ⅰ)the therapeutic effects of different doses of recombinant human prourokinase(rh-proUK)on patients with ST segment elevation myocardial infarction(STEMI)undergoing percutaneous coronary inter-vention(PCI),and ⅱ)its impact on peripheral blood P-selectin(CD62p)and Adropin levels.Methods:This randomized control study enrolled 132 STEMI patients undergoing PCI in Weinan Second Hospital between June 2020 and June 2023.Patients were randomly divided into control group(n=44,routine medication),low dose group(n=44,10 mg rh-proUK therapy)and high dose group(n=44,20 mg rh-proUK therapy).Therapeutic effective rate,myocardial perfu-sion immediate after operation,cardiac function,peripheral blood CD62p and Adropin levels,incidence of major adverse cardiovascular events(MACE)within 1 month after operation were compared among three groups.Results:Compared to patients in control group,those in high dose group had significantly higher total effective rate(95.5％vs.54.6％),pro-portions of TIMI myocardial perfusion grade(TMPG)grade 3(86.4％vs.25.0％)and ST segment resolution above 30％(∑STR≥30％)(88.6％vs.59.1％),stroke volume(SV)[(76.81±24.47)ml vs.(61.89±14.84)ml]and cardiac output(CO)[(6.48±1.45)L/min vs.(5.48±1.98)L/min],and significantly lower corrected TIMI frame count(CT-FC)[(31.80±6.32)frames vs.(52.39±7.14)frames],CD62p[(70.52±9.54)％vs.(82.42±12.44)％],Adropin[(82.48±9.55)pg/ml vs.(94.48±10.53)pg/ml]and total incidence of MACE(9.1％vs.38.6％)(P＜0.05 or＜0.01).Compared to those in low dose group,patients in high dose group had significantly higher total effective rate,pro-portions of TMPG grade 3 and ∑STR≥30％,SV and CO,and significantly lower CTFC,CD62p,Adropin and total inci-dence of MACE(P＜0.05 or＜0.01).Conclusion:The therapeutic effect of 20 mg rh-proUK on STEMI patients under-going PCI is significantly better than that of 10 mg,which could improve cardiac function,reduce CD62p,Adropin levels,and incidence of major adverse cardiovascular events.

Objective To investigate the effects of edaravone-dexborneol combined with intravenous thrombolysis on cerebrovascular reserve capacity and inflammatory factors in patients with acute cerebral infarction.Methods From January 2023 to June 2024,100 patients diagnosed with acute cerebral infarction in our hospital were divided into research group(n=50)and conventional group(n=50)by random number table method.The conventional group received intravenous thrombolysis,while the research group was treated with edaravone-dexborneol in addition to intravenous thrombolysis.The efficacy was evaluated after 2 weeks of treatment;the neurological function scores(mRS and NIHSS),cerebrovascular reserve indicators[pulsatility index(PI),cerebrovascular reserve(CVR)],hemorheological indicators(platelet aggregation rate,red blood cell aggregation index),levels of inflammatory factors[matrix metalloproteinase(MMP)-9,monocyte chemoattractant protein(MCP)-1,intercellular adhesion molecule(ICAM)-1],and levels of neurological functional factors[neuron specific enolase(NSE),nerve growth factor(NGF),central nervous system specific protein(S100)β]before and after treatment were compared.Results After 2 weeks of treatment,the efficacy of the conventional group was 80.00％,the efficacy of the research group was 94.00％.And the therapeutic effect of research group was significantly higher than the conventional group(x2=4.332,P=0.037).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower than those before treatment in the two groups,while the CVR and serum NGF levels were significantly higher than those before treatment(all P＜0.05).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower in the research group than those in the conventional group(all P＜0.05),while the CVR and serum NGF level were significantly higher in the research group than those in the conventional group(all P＜0.05).Conclusion The combination of edaravone-dexborneol with intravenous thrombolysis can improve clinical efficacy,restore neurological function,enhance cerebrovascular reserve capacity,improve hemorheology,and reduce inflammatory factors in patients with acute cerebral infarction.

Liver transplantation is a crucial treatment for end-stage liver disease,yet its complexity continues to limit clinical application.With the development of the internet and big data,artificial intelligence(AI)technologies have gradually expanded their use in liver transplantation surgery,covering donor liver evaluation,organ allocation,robot-assisted surgery,and postoperative management,demonstrating significant advantages.However,the application of AI also raises a series of ethical issues,notably fairness in resource allocation,conflicts between technical limitations and the principle of non-maleficence,ambiguous responsibility attribution,patient privacy security,and informed consent.This article systematically reviews the current applications of AI in liver transplantation surgery and the related ethical challenges,aiming to provide a reference for its rational use and sustainable development.

Objective To explore the method for grading the degree of uterine adhesion in a rat model.Methods A rat model of uterine adhesion was established using the double-injury method.Paraffin sections were observed using HE staining and Masson staining to compare morphological changes in the uterus,endometrial thickness,gland and vessel counts,uterine cavity area,and adhesion severity.Rat sections were classified into three grades based on uterine cavity area for comparative analysis.Results The average uterine cavity area and uterine cavity area/endometrial layer area were smaller in rats in the model group compared with the blank group(P＜0.01).The uterine cavity area/endometrial layer area ratio was categorized into grades Ⅰ,Ⅱ,and Ⅲ,with a significant difference among the grades(P＜0.05,P＜0.01).Conclusions The uterine cavity area/endometrial layer area ratio may reflect the grading difference in the degree of uterine adhesion in rats with uterine adhesions.This ratio may thus be used as a grading-evaluation criterion in the rat model of uterine adhesion,with implications for diagnostic grading in this model.