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 investigate the correlation between liver stiffness and histopathological changes in a rat model of acute hepatitis using virtual touch tissue imaging quantification (VTIQ) technology.Methods:A total of 100 SPF-grade SD rats were randomly divided into 3 groups: control ( n=30), low-dose ( n=35), and high-dose ( n=35) groups. Acute hepatitis models were induced in the low-dose and high-dose groups using 400 mg/kg and 600 mg/kg of Thioacetamide (TAA), respectively. Liver stiffness parameters of the right median lobe and right lobe were measured using VTIQ technology, Mean-H and Mean-L represent the liver lobes with higher and lower liver stiffness measurments, respectively, while Mean represent the average of the measurements from both liver lobes. Comparative analyses of liver stiffness parameters were performed across three groups and between the two lobes of the liver. The correlations between the Mean values of liver stiffness and semi-quantitative histopathological data were investigated. Ten rats were randomly selected from each of the 3 groups to test the repeatability of VTIQ values before and after euthanasia with intraperitoneal anesthesia. Subsequently, 10 rats after euthanasia from each 3 group were randomly chosen to assess the repeatability of VTIQ measurements for inter-observer and intra-observer variabilities. Results:VTIQ results showed statistically significant differences in Mean, Mean-H, and Mean-L among the 3 groups (all P<0.01). The high-dose group had higher measurements compared to the low-dose and control groups, with significant intergroup differences (all P<0.01). Significant differences in Mean-H and Mean-L were observed between the two liver lobes in both low and high-dose groups (all P<0.01). The Mean value showed significant positive correlations with semi-quantitative histopathological data of hepatocellular edema, periportal inflammatory cell infiltration, macrophage proliferation, and bile duct proliferation ( r=0.391, 0.648, 0.577, 0.542; all P<0.01). Multivariate linear regression analysis indicated that hepatocellular edema, eosinophilic change, and bile duct proliferation significantly and positively predicted the Mean value (β=-0.278, -0.196, -0.333; all P<0.05). There were no significant differences of VTIQ measurements befor and after euthanasia (all P>0.05), with repeatability coefficients of 0.166, 0.182, 0.185 for Mean, Mean-H, and Mean-L, respectively. Post-euthanasia, inter- and intra-observer VTIQ differences remained non-significant (all P>0.05), with Mean, Mean-H, Mean-L coefficients of 0.114, 0.194, 0.165 and 0.206, 0.322, 0.268, respectively. Conclusions:VTIQ technology demonstrates potential clinical value in assessing a rat model of acute hepatitis, offering a new perspective for non-invasive evaluation of acute hepatitis. However, its clinical application requires further validation.

AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.

Objective:To explore the clinical effect of a pedicled gracilis musculocutaneous flap on reconstruction of chronic sinus wounds in inguinal region.Methods:From September 2015 to June 2023, 10 patients with chronic inguinal sinus wounds were treated in Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. The patients were 6 males and 4 females, aged 15-72 years old with an average age of 45 years old. Causes of injury: 4 patients were of non-healed wound after inguinal lymph node dissection for external genital or penile cancer, 2 of chronic radiation ulcers formed in the inguinal area after radiotherapy, 2 of femoral artery angiography site non-healing after lower limb artery balloon angioplasty, 1 of wound non-healing after resection of inguinal protuberant skin fibrosarcoma, and 1 of non-healing ulceration after repeated scratching due to inguinal pruritus. The wounds were all chronic in the groin region, all with a course over 30 days and sinus formation. Soft tissue defects on the surface of wounds ranged from 2.0 cm × 3.0 cm to 5.0 cm × 7.0 cm, and the depth of the sinus was from 2.0 cm to 5.0 cm. After debridement, ipsilateral gracilis musculocutaneous flaps were taken for defect reconstruction. Size of the flaps was 3.5 cm × 4.0 cm - 8.0 cm × 9.0 cm, the length of the gracilis musculocutaneous composite flaps was 16.0 - 24.0 cm, and the volume of the flap was 96.0 - 180.0 cm 3. The gracilis tissue of the flap was filled into the sinus tract and the wound was covered by the cutaneous tissue of the flap. Donor sites of the flap were pulled together and directly sutured. After surgery, hip movements were avoided and appropriately raised the affected limb, observed the survival of gracilis musculocutaneous flap as well as the healing of donor site. Scheduled postoperative follow-ups were conducted through the visits of outpatient clinic and interviews via WeChat or Internet hospital. Results:All the flaps survived. One flap had bleeding at the edge of flap within 24 hours after surgery and resulted in suture dehiscence. After bedside haemostasis, debridement and re-suture, it was healed. All donor sites achieved primary healing. All of the 10 patients were included in the postoperative follow-up for 6-21 months, with an average of 13 months. The flaps were in good colour and appearance, and the patients were satisfactory with the appearance. Scars were seen in the donor sites, but there was no obvious functional impairment. During the follow-up, no flap rupture occurred.Conclusion:The pedicled gracilis musculocutaneous flap is used to reconstruction of chronic inguinal sinus wounds, which can fully fill the sinus tract and simultaneously reconstruct the soft tissue defect of wound. This surgery is simple, practical and with good clinical efficacy.

Objective:To investigate the clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects.Methods:The study was a retrospective observational study. From July 2017 to March 2023, 21 patients with stage Ⅲ or Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 13 males and 8 females, aged 14-84 years. There were 31 ischial tuberosity pressure ulcers, with an area of 1.5 cm×1.0 cm-8.0 cm×6.0 cm. After en bloc resection and debridement, the range of skin and soft tissue defect was 6.0 cm×3.0 cm-15.0 cm×8.0 cm. According to the depth and size of sinus tract and range of skin and soft tissue defects on the wound after debridement, the wounds were repaired according to the following three conditions. (1) When there was no sinus tract or the sinus tract was superficial, with a skin and soft tissue defect range of 6.0 cm×3.0 cm-8.5 cm×6.5 cm, the wound was repaired by direct suture, Z-plasty, transfer of buttock local flap, or V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. (2) When the sinus tract was deep and small, with a skin and soft tissue defect range of 8.5 cm×4.5 cm-11.0 cm×6.5 cm, the wound was repaired by the transfer and filling of gracilis muscle flap followed by direct suture, or Z-plasty, or combined with transfer of inferior gluteal artery perforator flap. (3) When the sinus tract was deep and large, with a skin and soft tissue defect range of 7.5 cm×5.5 cm-15.0 cm×8.0 cm, the wound was repaired by the transfer and filling of gracilis muscle flap and gluteus maximus muscle flap transfer, followed by direct suture, Z-plasty, or combined with transfer of buttock local flap; and transfer and filling of biceps femoris long head muscle flap combined with rotary transfer of the posterior femoral cutaneous nerve nutrient vessel flap; and filling of the inferior gluteal artery perforator adipofascial flap transfer combined with V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. A total of 7 buttock local flaps with incision area of 8.0 cm×6.0 cm-19.0 cm×16.0 cm, 21 gracilis muscle flaps with incision area of 18.0 cm×3.0 cm-24.0 cm×5.0 cm, 9 inferior gluteal artery perforator flaps or inferior gluteal artery perforator adipofascial flaps with incision area of 8.5 cm×6.0 cm-13.0 cm×7.5 cm, 10 gluteal maximus muscle flaps with incision area of 8.0 cm×5.0 cm-13.0 cm×7.0 cm, 2 biceps femoris long head muscle flaps with incision area of 17.0 cm×3.0 cm and 20.0 cm×5.0 cm, and 5 posterior femoral cutaneous nerve nutrient vessel flaps with incision area of 12.0 cm×6.5 cm-21.0 cm×10.0 cm were used. The donor area wounds were directly sutured. The survival of muscle flap, adipofascial flap, and flap, and wound healing in the donor area were observed after operation. The recovery of pressure ulcer and recurrence of patients were followed up.Results:After surgery, all the buttock local flaps, gracilis muscle flaps, gluteus maximus muscle flaps, inferior gluteal artery perforator adipofascial flaps, and biceps femoris long head muscle flaps survived well. In one case, the distal part of one posterior femoral cutaneous nerve nutrient vessel flap was partially necrotic, and the wound was healed after dressing changes. In another patient, bruises developed in the distal end of inferior gluteal artery perforator flap. It was somewhat relieved after removal of some sutures, but a small part of the necrosis was still present, and the wound was healed after bedside debridement and suture. The other posterior femoral cutaneous nerve nutrient vessel flaps and inferior gluteal artery perforator flaps survived well. In one patient, the wound at the donor site caused incision dehiscence due to postoperative bleeding in the donor area. The wound was healed after debridement+Z-plasty+dressing change. The wounds in the rest donor areas of patients were healed well. After 3 to 15 months of follow-up, all the pressure ulcers of patients were repaired well without recurrence.Conclusions:After debridement of ischial tuberosity pressure ulcer, if there is no sinus tract formation or sinus surface is superficial, direct suture, Z-plasty, buttock local flap, or V-Y advancement repair of posterior femoral cutaneous nerve nutrient vessel flap can be selected according to the range of skin and soft tissue defects. If the sinus tract of the wound is deep, the proper tissue flap can be selected to fill the sinus tract according to the size of sinus tract and range of the skin and soft tissue defects, and then the wound can be closed with individualized flap to obtain good repair effect.

Objective:To investigate the characteristics and surgical management of mesh infection after tension-free repair of inguinal hernia.Methods:The clinical and follow-up data of 87 patients with mesh infection after tension-free repair of inguinal hernia at the Department of Hernia and Abdominal Wall Surgery,Beijing Chaoyang Hospital from 2018 to 2020 were retrospectively analyzed.Results:The most frequent type of repair was plug implantation, accounting for 57.5% of the procedures. The most common clinical presentation was a chronic sinus. 79.3% patients had a >3-month history of chronic infection. Staphylococcus aureus was the most common bacteria. All patients underwent open debridement. Fifty-one patients had a complete removal of the infected mesh, and 36 had partial removal. All patients were followed up for 18.7-54.2 months. There was no significant difference in the incidence of wound infection, seroma, hematoma, inguinal hernia recurrence, and chronic pain between those with complete removal and that partial removal (all P>0.05). Seventeen cases suffered recurrent sinus in the partial mesh removal group, and the incidence was significantly higher than that in the complete mesh removal group ( P<0.001). Conclusion:Infected mesh removal is an effective treatment for mesh infection after tension-free repair of inguinal hernia and should be removed as completely as possible.

Objective:To investigate the surgical treatment of mesh infection after lapa-roscopic inguinal hernia repair.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with mesh infection after laparoscopic inguinal hernia repair who were admitted to the Affiliated Beijing Chaoyang Hospital of Capital Medical University from January 2018 to December 2020 were collected. There were 30 males and 2 females, aged 59(range, 19-81)years. All patients underwent debridement. Observation indicators: (1) surgical and postopera-tive situations; (2) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between was conducted using Fisher exact probability. Results:(1) Surgical and postoperative situations. All 32 patients underwent debridement success-fully, with the operation time and volume of intraoperative blood loss as 110(range, 45-220)minutes and 24(range, 5-200)mL. Of the 32 patients, there were 6 cases undergoing open debridement, 26 cases undergoing laparoscopic exploration with 12 cases clarified the cause of infection, in which 4 cases had intestinal fistula by mesh infection breaking through the peritoneum and invading the intestinal tract and underwent laparoscopic intestinal fistula repair, 3 cases had significant amount of residual medical glue, 3 cases had mesh wrinkling and curling, 2 cases underwent peritoneum suturing with black silk thread. There were 18 cases undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal. There were 18 cases undergoing removal of infected mesh by laparoscopic posterior approach and 14 cases undergoing removal of infected mesh by open anterior approach. Twenty-nine of the 32 patients had bacterial culture and drug allergy testing, including 24 cases with positive cultures, while 5 cases with negative cultures. The duration of hospital stay of the 32 patients was 27.0(range, 9.0-85.0)days. (2) Follow-up. All 32 patients were followed up for 37.9(range, 18.7-52.5)months. There were 5 cases and 2 cases with postoperative incision infection in the 18 patients undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). There were 7 cases, 4 cases with seroma, recurrent sinus in the 18 patients undergoing complete removal of infected mesh and 5 cases, 6 cases in the 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). None of patient in the two groups had hematoma, recurrent inguinal hernia or chronic pain. The 7 patients with incision infec-tion recovered effectively after symptomatic treatment. The 12 patients with seroma received no special treatment. The 10 patients with recurrent sinus underwent debridement, in which 9 cases did not experience any further abdominal wall infections and 1 case underwent the third debride-ment. Conclusion:The management of mesh infection following laparoscopic inguinal hernia repair necessitates the expertise of hernia specialists to complete remove the infected mesh or partial remove the infected mesh based on the specific clinical scenario.

Objective:To investigate the application value of combined open and laparos-copic incisional hernia repair (hereinafter referred to as hybrid technique) in the treatment of recurrent incisional hernia.Methods:The retrospective and descriptive study was conducted. The clinical data of 36 patients with recurrent incisional hernia who were admitted to the Affiliated Beijing Chaoyang Hospital of Capital Medical University from January 2015 to December 2021 were collected. There were 10 males and 26 females, aged 62(range, 25-83)years. All patients underwent incisional hernia repair using the hybrid technique. Observation indicators: (1) intraoperative situa-tions; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All 36 patients did not undergo component separation and successfully closed the hernia defect before completing the surgery. The operation time, defect area and area of mesh of the 36 patients were (102±41)minutes, (73±39)cm 2 and 300(range, 150-600)cm 2. Of the 36 patients, 9 cases required complete removal of the previous mesh, 2 cases had partial removal of the previous mesh and 25 cases did not require mesh removal. Two of the 36 patients had intestinal serosal tears, which needed suture repair during the operation. (2) Postoperative situations. Eight of the 36 patients had post-operative complications, including 6 cases of seroma, 1 case of subcutaneous hematoma and 1 case of undetected iatrogenic intestinal injury during the operation. The duration of the postoperative hospital stay of the 36 patients was 14(range, 7-57)days. (3) Follow-up. All 36 patients were followed up for 64 (range, 13-96)months. During the follow-up period, 2 cases had hernia recurrence and 1 case had intestinal obstruction. Conclusion:The hybrid technique in the treatment of recurrent incisional hernia is safe and feasible.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.