Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective:To explore the clinical effect on the treatment of radiation induced deep ulcers in the inguinal region with ipsilateral anterolateral thigh chimeric perforator flap.Methods:From March 2020 to March 2024, retrospective analysis of 8 patients with radiation induced deep ulcers in the inguinal region were treated with ipsilateral anterolateral thigh chimeric perforator flap in the Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. All ulcers induced by radiation were caused by postoperative radiotherapy in the inguinal region, of which 4 were of vulvar or penile cancer, 2 of urinary tract tumour, 1 of inguinal protuberant dermatofibrosarcoma and 1 of myofibroblastic sarcoma in lower abdominal wall. The course of the radiation induced ulcer was 0.5-11.0 years, with an average of 2.9 years. The sizes of the ulcerative wound were 2.5 cm × 3.0 cm - 5.5 cm × 7.5 cm. Preoperative biopsies of the tissues around wound and pelvic CT scans were performed to preliminarily exclude a tumour recurrence or an ulcerative malignancy, as well as to confirm the depth of radiation ulcer. The wound size after debridement was 4.5 cm × 6.0 cm-13.5 cm × 19.0 cm, with a depth of 2.0-4.0 cm. An ipsilateral anterolateral thigh chimeric perforator flap was transferred to reconstruct the wound, after the wound edges were cleared from tumour through intraoperative frozen section examinations. The flaps were 5.5 cm × 7.0 cm - 14.0 cm × 20.0 cm in size, with the volumes of muscle flap at 7.0 cm × 4.0 cm × 3.0 cm - 14.0 cm × 7.0 cm × 3.0 cm. After having the deep defect at the base of wound filled with a muscle flap, the wound surface was covered by the flap. Four patients had direct suture of the donor sites and 4 received a thick skin graft of head or contralateral thigh grafting. Survival of the anterolateral thigh chimeric perforator flaps and the healing of donor sites were observed after surgery through scheduled postoperative follow-up by the visits of outpatient clinic and distant interviews via telephone, WeChat or the internet hospital.Results:One of the ipsilateral anterolateral thigh chimeric perforator flaps had venous occlusion within 24 hours after surgery. Emergency surgical exploration revealed that it was caused by a haematoma compression due to haemorrhage in the muscle flap. Further debridement, haemostasis and suture were performed, then the wound healed. The rest of 7 flaps all survived. All donor sites healed primarily. The postoperative follow-up lasted for 5-17 months with all of the 8 patients, at 8.4 months in average. Both the donor and recipient sites healed well without recurrence of radiation ulcer in the affected sites. The appearance and texture of the flaps were good, and there was no obvious functional impairment at the donor sites.Conclusion:The treatment of radiation induced deep ulcer in the inguinal region with an ipsilateral anterolateral thigh chimeric perforator flap has shown good results, without recurrence of ulcer after surgery. The appearance and texture of the affected sites are good, and there is no secondary functional impairment at the donor site.

Objective:To explore the application strategies and clinical effects of superior gluteal artery perforator tissue flaps in repairing stage Ⅳ pressure ulcers in the sacrococcygeal region.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 89 patients with stage Ⅳ pressure ulcers in the sacrococcygeal region who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 59 males and 30 females, aged 21 to 84 years. There were 89 sacrococcygeal pressure ulcers, with an area of 5.0 cm×4.0 cm-21.0 cm×21.0 cm after debridement. According to the shape, size, and depth of the wounds after debridement, combined with the elasticity and texture of the skin around the wounds, and the principle of minimizing damage to the donor area, the appropriate forms of superior gluteal artery perforator tissue flaps were cut for wound repair in the following three conditions. (1) For wounds with a round shape, an area of 5.0 cm×5.0 cm-21.0 cm×21.0 cm, and a depth of 1.0-3.5 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, bilobed superior gluteal artery perforator relay flap, and bilateral superior gluteal artery perforator rotational flap were used. (2) For wounds with an oval shape, an area of 5.0 cm×4.0 cm-18.5 cm×10.5 cm, and a depth of 1.0-3.0 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, unilateral superior gluteal artery perforator propeller flap combined with contralateral superior gluteal artery perforator V-Y advanced flap or keystone flap were used. (3) For wounds with a fusiformis shape, an area of 7.0 cm×4.0 cm-17.5 cm×6.0 cm, and a depth of 1.5-5.0 cm, the unilateral or bilateral superior gluteal artery perforator V-Y advanced flap, superior gluteal artery perforator keystone flap, or superior gluteal artery perforator keystone flap combined with gluteus maximus muscle flap were used. In this group of patients, a total of 40 superior gluteal artery perforator propeller flaps (with an resection area of 11.0 cm×6.0 cm-17.0 cm×11.0 cm), 22 superior gluteal artery perforator propeller myocutaneous flaps (with an resection area of 10.0 cm×5.0 cm-14.0 cm×8.0 cm), 7 bilobed superior gluteal artery perforator relay flaps (with a main flap resection area of 5.5 cm×5.5 cm-18.0 cm×11.5 cm and a side flap resection area of 4.5 cm×3.0 cm-11.0 cm×6.5 cm), 5 bilateral superior gluteal artery perforator rotational flaps (with a total resection area of 20.0 cm×16.0 cm-26.0 cm×21.0 cm on both sides), 14 superior gluteal artery perforator V-Y advanced flaps (with an resection area of 12.0 cm×10.0 cm-18.0 cm×18.0 cm), 13 superior gluteal artery perforator keystone flaps (with an resection area of 13.0 cm×6.5 cm-19.0 cm×18.0 cm), and 3 gluteus maximus muscle flaps (with an resection area of 8.0 cm×3.0 cm-15.0 cm×4.5 cm). The donor area wounds were all directly sutured. The survival of tissue flaps was observed and the incidence rate of delayed wound healing in the reception area was calculated, and wound healing in the donor area was observed. The appearance and texture of tissue flaps and recurrence of pressure ulcers were followed up.Results:After surgery, all bilateral superior gluteal artery perforator rotational flaps, superior gluteal artery perforator V-Y advanced flaps, superior gluteal artery perforator keystone flaps, and gluteus maximus muscle flaps survived well. There were 6 cases of delayed wound healing in the reception area after surgery, with an incidence rate of 6.7% (6/89). Two patients had incision dehiscence in the donor area wounds due to postoperative bleeding, the wounds healed after debridement, vacuum sealing drainage, and dressing change. The wounds in the donor area of the remaining patients healed well. Six patients were lost to follow-up. Eighty-three patients were followed up for 3-48 months, of whom 4 patients died. Among the remaining 79 patients, 3 cases had pressure ulcers recur due to improper nursing, while the rest of the patients had tissue flaps with good appearance and soft texture and no recurrence of pressure ulcers.Conclusions:Based on the characteristics of wound shape, size, and depth after debridement of stage Ⅳ pressure ulcers in the sacrococcygeal region, individualized selection of flap, myocutaneous flap, or a combination of flap and gluteus maximus muscle flap based on the perforating branch of the superior gluteal artery perforator can achieve good clinical repair results. The postoperative tissue flap survived well, with a good appearance, soft texture, and less recurrence of pressure ulcers.

Objective:To investigate the feasibility and clinical outcomes of using the deep inferior epigastric perforator flap to repair stage Ⅳ pressure ulcers in elderly patients with the femoral trochanter.Methods:Retrospective analysis of clinical data of elderly patients with stage Ⅳ pressure ulcers of the femoral trochanter treated at the Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University from May 2018 to May 2023 using the deep inferior epigastric perforator flap.The deep inferior epigastric perforator flap was designed on the same side of the abdomen based on the preoperative detection of the paraumbilical perforating branch.The axis of the inferior epigastric artery was determined by the line connecting the femoral artery pulsation point at the inguinal ligament and the obvious paraumbilical perforating branch point. The axis of the skin flap was determined by the line connecting the obvious paraumbilical perforating branch point and the subscapular angle. Combined with the situation of the sinus after pressure ulcer debridement and the range of skin and soft tissue defects, the inferior epigastric artery perforating branch skin flap was cut and repaired. The pedicle of the inferior epigastric artery was freed to the required length according to the location of the pressure ulcer, and the wound was transferred and repaired through a subcutaneous tunnel. The donor area was directly pulled and sutured. The survival of the skin flap and the healing of the donor site wound after surgery were observed, and the recurrence of pressure ulcers, the appearance and texture of the skin flap, and the recovery of the donor site were followed up regularly.Results:A total of 11 patients were included, including 7 males and 4 females; age ranged from 66 to 83 years old, with an average of 72.1 years old. There were total of 11 pressure ulcers in the femoral trochanter, with an area of 5.0 cm × 3.0 cm-13.0 cm ×6.0 cm before debridement and an area of 8.0 cm × 5.0 cm-16.0 cm × 8.0 cm after debridement. The deep inferior epigastric perforator flap was used to repair the wound. The flap was cut with an area of 10.0 cm × 6.0 cm-18.0 cm × 9.0 cm, and the length of the blood vessels in the flap pedicle was 12-16 cm, with an average of 14 cm. After surgery, 9 of the 11 flaps survived completely. One skin flap developed purplish discoloration at the distal end 24 hours after surgery, which was relieved by removing the suture at the site with high tension at the wound edge. One skin flap also showed slight necrosis at the distal end. The flap was removed under local anesthesia at the bedside of the ward, and the surgical wound was directly sutured. After dressing change, it healed. The wounds in the donor area all healed well. Follow up for 3-15 months postoperatively, with an average of 11 months, showed no recurrence of pressure ulcers in all patients. The skin flap had a soft texture, and its color and appearance were similar to those of the surrounding skin. No abdominal wall hernia was observed in the inferior epigastric donor area.Conclusion:The deep inferior epigastric perforator flap has a long vascular pedicle, reliable blood supply, sufficient tissue volume for cutting, no recurrence of pressure ulcers after surgery, good appearance and texture of the affected area, and no secondary abdominal wall hernia in the donor site. It is an effective method for repairing stage Ⅳ pressure ulcers of the femoral trochanter in elderly patients.

AIM:To investigate the effects of macrophage galactose-type lectin 1(Mgl1)gene deletion on he-matopoietic stem/progenitor cells(HSPCs)under steady-state conditions and inflammation.METHODS:Mice were di-vided into a control group(wild-type)and an experimental group(Mgl1 gene-deleted).Flow cytometry was used to ana-lyze the proportions of various hematopoietic cell lineages in the peripheral blood and bone marrow of both groups,assess-ing the impact of Mgl1 gene deletion on steady-state hematopoiesis(n=3～4).Transplantation and colony-forming assays were utilized to evaluate the effects of Mgl1 gene deletion onthe repopulation capacity and colony-forming ability of HSPCs(n=5).The LPS-induced inflammation model was employed to examine the effects of Mgl1 gene deletion on the inflamma-tory response of HSPCs both in vitro and in vivo(n=5～8).Western blot and RT-qPCR were conducted to analyze the alter-ations in signaling pathways regulated by Mgl1 in the inflammatory response of HSPCs(n=3).RESULTS:(1)Mgl1 gene deletion had no significant effecton steady-state hematopoiesis(P>0.05).(2)Mgl1 gene deletion promoted inflam-mation-induced cell differentiation of HSPCs(P<0.01).(3)Mgl1 gene deletion accelerated the exhaustion of HSPCs un-der prolonged inflammatory conditions(P<0.01).(4)Mgl1 was found to regulate the inflammatory response of HSPCs via the NF-κB signaling pathway.CONCLUSION:Mgl1 gene deletion enhances the inflammatory response of HSPCs via the NF-κB signaling pathway.

Objective To investigate the application value of conventional MRI combined with diffusion tensor imaging(DTI)in evaluating the correlation between the texture composition of benign prostatic hyperplasia(BPH)and the International Prostate Symptom Score(IPSS).Methods Seventy patients with BPH confirmed by pathology were retrospectively analyzed and all patients underwent conventional MRI,DTI and IPSS before surgery.Evaluation metrics included:the mean signal intensity of T2WI(mean-SI-T2WI),apparent diffusion coefficient(ADC)and fractional anisotropy(FA)values.Independent samples t-test,partial correlation analysis,and receiver operating characteristic(ROC)curve were used to assess the correlation between the texture parameters of the prostate transition zone and IPSS.Results The mean-SI-T2WI was significantly negatively correlated with IPSS(r=-0.683,P<0.001);the average ADC value was slightly negatively correlated with IPSS(r=-0.467,P<0.001);and the average FA value was slightly positively correlated with IPSS(r=0.419,P<0.001).The predictive value of MRI texture parameters for IPSS in BPH patients,ranked from high to low,mean-SI-T2WI[area under the curve(AUC)=0.734],average ADC value(AUC=0.673),and average FA value(AUC=0.635);However,the combination of mean-SI-T2WI+ADC+FA(AUC=0.791)did not significantly improve the diagnostic efficacy by DeLong's test(P>0.05).Conclusion Mean-SI-T2WI,DWI and DTI can be used to evaluate the composition of the prostate,among which mean-SI-T2WI is the best,and the com-bination of them can not improve the diagnostic efficacy.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective To investigate the application value of conventional MRI combined with diffusion tensor imaging(DTI)in evaluating the correlation between the texture composition of benign prostatic hyperplasia(BPH)and the International Prostate Symptom Score(IPSS).Methods Seventy patients with BPH confirmed by pathology were retrospectively analyzed and all patients underwent conventional MRI,DTI and IPSS before surgery.Evaluation metrics included:the mean signal intensity of T2WI(mean-SI-T2WI),apparent diffusion coefficient(ADC)and fractional anisotropy(FA)values.Independent samples t-test,partial correlation analysis,and receiver operating characteristic(ROC)curve were used to assess the correlation between the texture parameters of the prostate transition zone and IPSS.Results The mean-SI-T2WI was significantly negatively correlated with IPSS(r=-0.683,P<0.001);the average ADC value was slightly negatively correlated with IPSS(r=-0.467,P<0.001);and the average FA value was slightly positively correlated with IPSS(r=0.419,P<0.001).The predictive value of MRI texture parameters for IPSS in BPH patients,ranked from high to low,mean-SI-T2WI[area under the curve(AUC)=0.734],average ADC value(AUC=0.673),and average FA value(AUC=0.635);However,the combination of mean-SI-T2WI+ADC+FA(AUC=0.791)did not significantly improve the diagnostic efficacy by DeLong's test(P>0.05).Conclusion Mean-SI-T2WI,DWI and DTI can be used to evaluate the composition of the prostate,among which mean-SI-T2WI is the best,and the com-bination of them can not improve the diagnostic efficacy.

AIM:To investigate the effects of macrophage galactose-type lectin 1(Mgl1)gene deletion on he-matopoietic stem/progenitor cells(HSPCs)under steady-state conditions and inflammation.METHODS:Mice were di-vided into a control group(wild-type)and an experimental group(Mgl1 gene-deleted).Flow cytometry was used to ana-lyze the proportions of various hematopoietic cell lineages in the peripheral blood and bone marrow of both groups,assess-ing the impact of Mgl1 gene deletion on steady-state hematopoiesis(n=3～4).Transplantation and colony-forming assays were utilized to evaluate the effects of Mgl1 gene deletion onthe repopulation capacity and colony-forming ability of HSPCs(n=5).The LPS-induced inflammation model was employed to examine the effects of Mgl1 gene deletion on the inflamma-tory response of HSPCs both in vitro and in vivo(n=5～8).Western blot and RT-qPCR were conducted to analyze the alter-ations in signaling pathways regulated by Mgl1 in the inflammatory response of HSPCs(n=3).RESULTS:(1)Mgl1 gene deletion had no significant effecton steady-state hematopoiesis(P>0.05).(2)Mgl1 gene deletion promoted inflam-mation-induced cell differentiation of HSPCs(P<0.01).(3)Mgl1 gene deletion accelerated the exhaustion of HSPCs un-der prolonged inflammatory conditions(P<0.01).(4)Mgl1 was found to regulate the inflammatory response of HSPCs via the NF-κB signaling pathway.CONCLUSION:Mgl1 gene deletion enhances the inflammatory response of HSPCs via the NF-κB signaling pathway.