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.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

'Injury but not disability, disability but not useless’ is the guiding principle behind the establishment of plastic and reconstructive surgery, making it a unique specialty in modern medicine. Its development relies not only on the optimized use of donor resources but also on technological advancements and innovations in concepts. However, in the face of severe tissue damage caused by burns, trauma, and congenital deformities, traditional repair method often fall short, necessitating more effective solutions. Against this backdrop, progress in donor sourcing and interdisciplinary innovation will inject new vitality into reconstructive surgery. In this context, we take facial transplantation reconstruction as a starting point, reviewing and organizing the technological development, issues, and challenges of autologous and allogeneic facial transplantation reconstruction from the perspective of donors. This exploration aims to shed light on the future direction of this field and gain a deeper understanding of the present and future of donor-driven reconstructive surgery.

Objective:To summarize the technical experience of using a contralateral free gracilis myocutaneous flap combined with an adductor magnus perforator flap for salvaging failure of breast reconstruction after transplantation with the free adductor magnus perforator flap.Methods:A retrospective analysis was conducted on patients with breast cancer who received contralateral posteromedial thigh flap (gracilis myocutaneous flap combined with adductor magnus perforator flap) transplantation for immediate unilateral breast reconstruction developed vascular crisis and caused flap necrosis at the Department of Oncology Plastic Surgery, Hunan Cancer Hospital, between December 2016 to December 2022. All patients with early-stage breast cancer received modified radical mastectomy. All patients were selected to undergo the immediate breast reconstruction surgery with unilateral free adductor magnus perforator flap transplantation. The proximal end of internal mammary vessels were used as the recipient vessels in all cases. After the emergency exploration confirmed the necrosis of the flap, a contralateral free gracilis myocutaneous flap combined with adductor magnus perforator flap were immediately harvested for salvage breast reconstruction. The vascular pedicle of the gracilis muscular branch and the adductor magnus perforator branch were anastomosed with the proximal and distal ends of the internal mammary vessels, respectively. Postoperative patient monitoring was conducted intensively, with follow-up assessments focusing on breast contour and donor site recovery.Results:A total of 5 patients were included, aged 26 to 42 years, with an average of (31.5±1.8) years. All salvaged breast reconstruction surgeries were successful, the salvaged flap measured 15.0 cm×6.0 cm×4.0 cm-17.0 cm×7.5 cm×5.5 cm. All the transplanted flaps survived after the operation, with satisfactory breast contour, good flap elasticity, and no contracture or deformation. The donor sites of both thigh flaps healed well, leaving only linear scars and no significant functional impairment to the lower limbs. Follow-up ranged from 9 to 24 months, with an average of 15.7 months. The breast shape was satisfactory, and there was no recurrence of breast cancer.Conclusion:The donor site morbidity of the posteromedial thigh flap is relatively small. When unilateral flap transplantation fails, immediate transfer of the contralateral flap can be chosen for salvage reconstruction. This approach ensures symmetrical donor site outcomes and is generally well-accepted by patients.

Objective:To explore the technical points and precautions of using bilateral free posteromedial thigh flap to reconstruct bilateral breasts.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent bilateral mastectomy and bilateral free posteromedial thigh flap transplantation for bilateral breast reconstruction at Hunan Cancer Hospital from June 2020 to January 2023. The operation was carried out simultaneously by two groups of doctors. Breast surgeons performed modified radical mastectomy for breast cancer or subcutaneous mastectomy. The flap group prepared bilateral free posteromedial thigh flaps. The posteromedial thigh flaps were designed in three patterns: transverse, vertical and oblique. The intrathoracal vessels were used as recipient vessels in all cases. There were two types of vascular anastomosis method: ① For flaps with single vascular pedicle, the artery was anastomosed with the proximal end of the internal thoracic artery, and the only accompanying vein was anastomosed with the proximal end of the internal thoracic vein, or the two accompanying veins were anastomosed with the proximal and distal ends of the internal thoracic vein; ② For flaps with dual vascular pedicles, arteries were anastomosed with the proximal and distal ends of the internal thoracic artery, and the accompanying veins on both sides communicated with the proximal and distal ends of the internal thoracic vein, respectively. Normal distribution measurement data were expressed as Mean±SD.Results:A total of 9 female patients were enrolled, aged 29 to 43 years, with an average age of 38.3 years. Among them, bilateral breast cancer was considered in 4 cases, unilateral breast cancer with multiple nodules in the opposite breast was in 3 cases, and bilateral multiple nodules along with high-risk of developing breast cancer suggested by gene testing were found in 2 cases. Modified radical mastectomy for breast cancer and nipple-sparing subcutaneous mastectomy were performed in 7 and 11 breasts, respectively. There were three design method for the posteromedial thigh flap: horizontal design (6 thighs); vertical design (6 thighs); diagonal design (6 thighs). A total of 18 posteromedial thigh flaps were raised. Four different types of posteromedial thigh flaps were used: gracilis muscle flap (6 thighs); great adductor muscle perforator flap (5 thighs); great adductor muscle flap (5 thighs); femoral gracilis flap+ adductor magnus flap (2 thighs). The skin flaps harvested were (18.9±0.6) cm in length, (7.2±0.4) cm in width and (4.2±0.3) cm in thickness. The average weight of the skin flaps were 235 grams (185-355 grams). The aforementioned vascular anastomosis method ① and ② were carried out in 15 and 3 breasts, respectively. The patients were followed up for 6 to 32 months, with an average of 17.3 months. All skin flaps survived, and the reconstructed breasts presented with good appearance, good elasticity, and no skin flap contraction or deformation occurred; scarring on the donor area was linear and mild; there was no significant impact on lower limb movement. The breast shape was satisfactory, and there was no recurrence of breast cancer.Conclusion:The application of bilateral free posteromedial thigh flap transplantation for reconstruction of bilateral breasts has flexible flap preparation and vascular anastomosis forms, which can achieve satisfactory result of bilateral symmetry.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P＜0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.