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

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective:To observe the clinical characteristics of esophageal reflux after total gastrectomy (ERATG), and to explore the mechanism of occurrence.Methods:Fourteen gastric cancer patients who underwent total gastrectomy were prospectively enrolled in this study. The postoperative symptoms were observed and recorded and 24 h MII-pH with pH monitoring was performed to investigate the characteristics of postoperative reflux.Results:After total gastrectomy patients were with different degrees of ERATG as heartburn, appetite loss, chest tightness and belching. The overall nature of ERATG is mainly weak acid, with a pH between 4 and 7. ERATG involved esophageal-jejunal anastomosis and a length of esophagus 7 cm above the anastomosis. Patients with typical reflux symptoms had a lower pH minimum in the upright position than those without typical symptoms[(4.76±0.71) vs.(5.68±0.37), t=2.866, P<0.05]. Patients with typical reflux symptoms had a higher frequency of reflux of mixed liquid and liquid-air reflux than those without typical symptoms[liquid(31.25±29.76) vs.(4.50±9.14), t=0.011, P<0.05; liquid-air(19.50±12.99) vs.(2.00±2.61), t=0.004, P<0.05]. Conclusion:ERATG is mainly a upward reflux of weakly acidic gas, with typical symptoms of heartburn, appetite loss, chest tightness and belching. Patients with typical symptoms usually have lower pH in the upright position.

Objective:To explore the treatment of iatrogenic injury to the medial collateral ligament (MCL) in total knee arthroplasty (TKA).Methods:From January 2009 to December 2016, 14 patients were treated at Department of Arthropathy, Zhengzhou Orthopedics Hospital for iatrogenic MCL injury in primary TKA (injury group). They were 3 males and 11 females with an age of (72.6±3.9) years. The MCL injury was body rapture in 9 cases and avulsion of femoral insertion in 5 ones. Interlacing suture was used for body rapture and reparative reconstruction with wire anchors or nails was performed for avulsion of femoral insertion. A restrictive condylar prosthesis was used instead in the 4 patients whose medial stability failed to be restored after repair of body rapture. A control group of 21 cases was enrolled who had suffered from no iatrogenic MCL injury in primary TKA at the corresponding period. There were 5 males and 16 females with an age of (73.2±3.9) years. The 2 groups were compared in terms of American Knee Society Score (KSS) and knee flexion.Results:There was no significant difference between the 2 groups in preoperative general data, showing comparability between groups ( P>0.05). The injury group was followed up for 18 to 36 months (mean, 33 months). Joint loosening was observed at 18 months after operation in 3 patients with nonrestrictive prosthesis who had to receive secondary revision. At the 36-month follow-up of the remaining 11 patients, normal knee extension and flexion was observed, the stress test of valgus showed no inner relaxation, their KSS increased significantly from preoperative 50.0±22.7 to 93.3±4.7, and their knee flexion was improved significantly from 90.4°±10.3° to 110.7°±8.8° ( P<0.05). There were no significant differences in KSS score or knee flexion between the 2 groups at 3, 6, 12 or 36 months after operation ( P>0.05). Conclusion:Iatrogenic MCL injury in primary TKA should be repaired and reconstructed by one-stage surgery because the patients can achieve curative results similar to those for the patients free from iatrogenic MCL injury in primary TKA.

Objective:To determine the diagnostic value of tumor markers in peritoneal lavage fluid from colorectal cancer patients for tumor peritoneal metastasis.Methods:A total of 227 colorectal cancer patients who undergoing surgical treatment were included. 300 ml of peritoneal lavage fluid was irrigated immediately upon laparotomy for traditional cytology (PLC) testing, 134 patients were tested for tumor marker of peritoneal lavage fluid (pTM). Univariate analysis was performed to determine the risk factors for peritoneal metastasis; pTM ROC curve was used to determine the best cutoff value; paired chi-square test was used to compare the difference between PLC and pTM detection.Results:The positive rate of PLC was 12.3% (28/227). Age>65, stage T3 + , lymph node metastasis, mucinous adenocarcinoma and increased serum CA125, CA19-9 are related to peritoneal metastasis; The best cutoff value of pTM for peritoneal metastasis : pCEA 17.095 ng/dl, sensitivity 58.3%, specificity 93.9%; pCA19-9 4.515 U/ml, sensitivity 83.3%, specificity 80.0%; pCA125 303.2 U/ml, sensitivity 58.3%, specificity 95.7%; pCA-724 3.01 U/ml, sensitivity 66.7%, specificity 95.7%; The best cutoff value of pTM for peritoneal micrometastasis: pCA19-9 3.43 U/ml, sensitivity 100%, specificity 72.2%. The positive rate of pCA19-9 was 29.85%, which was higher than that of PLC (χ 2=2.00, P<0.05). Conclusion:Peritoneal metastasis of colorectal cancer is related to tumor T stage, lymph node metastasis, tumor pathological type, and increased serum CA125 and CA19-9; pTM has diagnostic value for peritoneal metastasis of colorectal cancer.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.