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

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

Objective:To introduce the application of highly selective arterial indocyanine green angiography (hereinafter referred to as highly selective arterial angiography) in the design of anterolateral thigh free flap.Methods:This study was a retrospective observational study. From November 2023 to April 2024, 29 patients with wounds in extremities which were repaired by anterolateral thigh free flaps designed under the assistance of highly selective arterial angiography and met the inclusion criteria were admitted to the Department of Hand Surgery and Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 26 males and 3 females, aged 16 to 71 years. The wound area after debridement ranged from 8.0 cm×4.5 cm to 27.0 cm×16.0 cm. During the surgery, highly selective arterial angiography was used to assist in flap design. The fluorescence development range of the source arteries or perforators of flaps was observed. The blood supply range of the source arteries or perforators of flaps was determined based on the fluorescence development of the skin, and the excision position of the flap was adjusted. The flap incision area ranged from 9.0 cm×6.0 cm to 29.0 cm×16.0 cm. During the surgery, the number of highly selective arterial angiography, the type of source artery of perforators for puncture, and changes in the excision position of flaps were observed and recorded. After surgery, the blood supply and survival of flaps, the healing of wounds and the survival of skin grafts in the flap donor sites, and the angiography-related complications were observed.Results:All the 32 flaps of 29 patients were successfully excised. The highly selective arterial angiography was performed 37 times, including 13 cases of puncture of the oblique branch of the lateral circumflex femoral artery, 6 cases of puncture of the descending branch, 8 cases of double puncture of the oblique and descending branches, and 2 cases of puncture of arteries from other branches. During the surgery, the excision position of 28 flaps did not change, the excision position of 3 flaps moved towards proximal extremity of the thigh, and the excision position of 1 flap moved towards distal extremity of the thigh. All the flaps survived successfully after the surgery, and there was no partial necrosis of the flaps at the proximal or distal ends. The wounds in the flap donor sites healed, and all skin grafts survived. No angiography-related complications occurred.Conclusions:Highly selective arterial angiography can be used to determine the blood supply range of the source artery and perforators of the anterolateral thigh free flaps during the surgery. It can evaluate the blood supply of flaps more intuitively and objectively. Its application in assisting flap design can avoid partial flap necrosis caused by unreasonable preoperative design to a certain extent, and it is safe and reliable.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P<0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P>0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

【Objective】 To investigate the safety, feasibility and clinical efficacy of modified anterior robot-assisted laparoscopic radical prostatectomy (RALRP) with preservation of Retzius space. 【Methods】 The clinical data of 10 patients who underwent RALRP using the modified anterior approach to preserve the Retzius space in our hospital during June 2021 and March 2022 were retrospectively analyzed, including the preoperative, intraoperative, postoperative and follow-up data. 【Results】 All operations were successful without conversion to open surgery. The average operation time (robotic arm operation time) was (98.6±47.7) min, blood loss (105.0±57.3) mL, postoperative drainage tube indwelling time (5.3±1.3) d, postoperative urinary catheter indwelling time (7.2±0.8) d, and postoperative hospital stay (9.2±2.2) d. Urinary continence was achieved immediately after removal of the urinary catheter in 6 patients, 2 patients recovered 2 weeks after extubation, and 2 patients recovered 3 months after extubation. Postoperative pathology showed pT2a stage in 1 case, pT2b stage in 2 cases, and pT2c stage in 7 cases; Gleason score was 6-7 points; all postoperative resection margins were negative. During the follow-up of 3-12 months, no tumor recurrence was observed, and no patient was readmitted due to surgical complications. 【Conclusion】 RALRP with modified anterior approach to preserve the Retzius space is safe and feasible, with no serious complications during and after surgery, and the early postoperative urinary continence effect is comparable to that of the posterior approach.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To investigate the curative effects of the superficial peroneal artery perforator flap carrying two and more homologous perforators in repairing hand and foot wounds.Methods:A retrospective observational study was conducted. From January to September 2021, 23 patients with hand and foot wounds combined with bone or tendon exposure who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 16 males and 7 females, aged 23 to 68 years. After expansion of the wound, the wound area was 3.0 cm×2.0 cm to 11.0 cm×4.0 cm. All the wounds were repaired with the superficial peroneal artery perforator flap carrying two and more homologous perforators. The area of the resected flap was 4.0 cm×2.0 cm to 12.0 cm×5.0 cm. All the wounds in donor areas were sutured directly. During the operation, the resection of the flap, the number and caliber of carried perforators, the caliber of superficial peroneal artery, the length of vascular pedicle, and the number of accompanying veins of the superficial peroneal artery were recorded. The survival of the flap, the occurrence of complications, and the wound healing in the donor area were observed after operation. The recovery of the donor and recipient areas was followed up. At the last follow-up, the comprehensive evaluation scale was used to evaluate the curative effect of flap repair, and the sensory grading scale was used to evaluate the sensory function of the recipient area.Results:Totally 24 flaps were successfully resected in surgical operations, carrying 56 superficial peroneal artery perforators in total, with the caliber of perforators of 0.20-0.70 mm. The calibers of all perforators carried by 7 flaps were smaller than 0.40 mm. Nineteen flaps carried 2 perforators each, 3 flaps carried 3 perforators each, 1 flap carried 4 perforators, and 1 flap carried 5 perforators. During the operation, the superficial peroneal artery was resected with a caliber of 0.40-1.50 mm, the vascular pedicle was 2-6 cm in length, and each superficial peroneal artery had two accompanying veins. After operation, all the flaps survived smoothly, no vascular crisis or distal necrosis occurred, and the wounds healed well in the donor area. During the follow-up of 6 to 10 months after operation, the color, texture, and elasticity of the recipient area were good. Among them, 6 recipient areas were thinned and reshaped because of bloating. There was only linear scar and no obvious scar hyperplasia or pigmentation in the donor area, without significant change in sensory or motor function. At the last follow-up, the curative effect evaluation of flap repair was excellent in 22 flaps and good in 2 flaps, and the sensory function evaluation of the recipient area was grade S 3 in 1 area and grade S 2 in 23 areas. Conclusions:The superficial peroneal artery perforator flap with two and more homologous perforators has sufficient and reliable blood supply and is effective in repairing hand and foot wounds. It provides an ideal solution for the clinical problem in which the original operation scheme is abandoned due to the existence of only multiple slender perforators of caliber smaller than 0.40 mm, and only a single perforator in the operative field that cannot satisfy the needs of the flap blood supply and recipient area.

Objective:To summarize the morphological characteristics of the transverse branch of lateral femoral circumflex artery (LFCA) using digital subtraction angiography (DSA) and explore its clinical significance.Methods:A retrospective observational study was conducted. From October 2020 to May 2021, 62 patients with soft tissue injuries in the extremities were hospitalized in Suzhou Ruihua Orthopedic Hospital, including 40 males and 22 females, aged from 20 to 72 years. DSA was performed in the lateral femoral region of patients before the anterolateral thigh flap transplantation, and in combination with imaging scale to observe and measure the general condition of the blood vessels and the occurrence (with the occurrence rate being calculated), source artery, location of the origin point, direction of course, and the location of the perforating point of the cutaneous perforator of the transverse branch of LFCA, and in addition to classify the morphological characteristics of the transverse branch.Results:DSA detection showed that the femoral artery, the deep femoral artery, and the branches of LFCA were clearly distinguishable in 62 patients. Transverse branches of LFCA were observed in 59 patients, including 52 cases with a single transverse branch, and 7 cases with double transverse branches. The occurrence rate of transverse branches was 95.2% (59/62). A total of 66 transverse branches of LFCA were observed, of which 3 originated from the deep femoral artery, and 63 originated from the LFCA. The origin point of the transverse branch was 6.5-12.7 cm away from the anterior superior iliac spine. The transverse branch which was approximately perpendicular to the long axis of the body, originated outwards, ran between the ascending branch of LFCA and the oblique branch of LFCA, and branched along the way, with the trunk running under the greater trochanter. The perforating point of the cutaneous perforator of the transverse branch was 8.0-18.0 cm away from the anterior superior iliac spine. In the classification of morphological characteristics of the transverse branch of LFCA, the most common type was the one that originated from the same trunk with other branches of LFCA, accounting for 50.0% (31/62), followed by the one that originated from the singular trunk of LFCA (12 cases) or deep femoral artery (3 cases), accounting for 24.2% (15/62); the special type accounted for 21.0% (13/62), including 7 cases of double transverse branches and 6 cases of the transverse branch originated from the same trunk with multiple other branches of LFCA; those with small/absent transverse branch only accounted for 4.8% (3/62). Among the above-mentioned common trunk relationship of two branches, those with shared trunk of ascending and transverse branches were most frequently observed, accounting for 77.4% (24/31); those with shared trunks of the transverse and oblique branches (5 cases) and the transverse and descending branches (2 cases) accounted for 22.6% (7/31) altogether.Conclusions:A high incidence rate of the transverse branch of LFCA is observed through DSA. The transverse branch originates from the lateral femoral artery approximately perpendicular to the long axis of the body, mainly from the same trunk with another main branch of LFCA, especially the ascending branch. This positioning analysis can provide an important reference for the design and resection of anterolateral femoral flaps.