1.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
2.Alleviation of hypoxia/reoxygenation injury in HL-1 cells by ginsenoside Rg_1 via regulating mitochondrial fusion based on Notch1 signaling pathway.
Hui-Yu ZHANG ; Xiao-Shan CUI ; Yuan-Yuan CHEN ; Gao-Jie XIN ; Ce CAO ; Zi-Xin LIU ; Shu-Juan XU ; Jia-Ming GAO ; Hao GUO ; Jian-Hua FU
China Journal of Chinese Materia Medica 2025;50(10):2711-2718
This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology*
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Receptor, Notch1/genetics*
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Signal Transduction/drug effects*
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Mice
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Animals
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Mitochondrial Dynamics/drug effects*
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Mitochondria/metabolism*
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Cell Line
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Reactive Oxygen Species/metabolism*
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Oxygen/metabolism*
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Cell Hypoxia/drug effects*
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Cell Survival/drug effects*
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Membrane Potential, Mitochondrial/drug effects*
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Humans
3.Current situation of medicinal animal breeding and research progress in sustainable utilization of resources.
Cheng-Cai ZHANG ; Jia WANG ; Yu-Jie ZHOU ; Xiao-Yu DAI ; Xiu-Fu WAN ; Chuan-Zhi KANG ; De-Hua WU ; Jia-Hui SUN ; Sheng WANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(16):4397-4406
Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals
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Breeding
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China
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Medicine, Chinese Traditional
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Conservation of Natural Resources
4.Comparison of the efficacy of unilateral nailing combined with bone cement reinforcement and bilateral nailing in the treatment of osteoporotic thoracolumbar fractures.
Yu-Liang LOU ; Guo-Ying CHEN ; Can-Feng WANG ; Hui FEI ; Guan-Rong SUN ; Ren-Fu QUAN ; Wei LI ; Feng HONG
China Journal of Orthopaedics and Traumatology 2025;38(2):134-149
OBJECTIVE:
To compare the efficacy of percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar fractures.
METHODS:
A retrospective case-control study was used to analyze the clinical data of 78 patients with osteoporotic thoracic and lumbar fractures admitted from October 2017 to May 2019. According to the surgical method, it was divided into percutaneous pedicle screw combined with unilateral nail placement combined with unilateral bone cement strengthening group(bone cement group) and percutaneous pedicle screw combined with bilateral nail placement(screw group). In the bone cement group, 40 patients included 16 males and 24 females, with a mean age of (62.1±8.1) years old. In the screw group, 38 patients included 18 males and 20 females with a mean age of (65.1±9.3) years old. The operation time, intraoperative blood loss, length of hospital stay and postoperative complications were compared between two groups. The kyphosis Cobb angle, anterior edge height ratio, central height ratio and pain visual analogue score(VAS) were compared.
RESULTS:
All patients were followed up for 25 to 36 months. The operation time (70.1±17.3) min of the cement group was shorter than that of the screw group (78.6±18.2) min(P<0.05). There were no significant differences in intraoperative blood loss and length of hospital stay(P>0.05). The VAS in the cement group 1 year 1.5±0.5 and the latest follow-up 0.5±0.3 after operation were lower than 1 year 1.8±0.3 and the latest follow-up 0.8±0.4 in the screw group(P<0.05). The kyphosis Cobb angle, anterior edge height ratio, central height ratio in bone cement group, 1 year (6.2±1.2)°, (86.6±3.5)%, (91.1±2.5)%, the last follow-up (6.4±0.7)°, (85.5±3.3)%, (90.5±6.3)% were better than that of the screw group 1 year (6.8±1.4)°, (83.1±2.4)%, (89.9±3.4)% and the latest follow-up (7.1±1.1)°, (82.6±4.1)%, (87.6±5.9)%(P<0.05). There were 3 cases of bone cement leakage in the cement group, all of which had no clinical symptoms;and 2 cases of pedicle screws were extracted in the screw group, and the screws were removed at the last follow-up.
CONCLUSION
Percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar compression fractures in the elderly can achieve satisfactory efficacy and effectively relieve the pain of patients, but the former internal fixation system is more stable, and the long-term follow-up can effectively maintain the height of the anterior middle column and the correction of kyphosis deformity, and the incidence of chronic low back pain is lower.
Humans
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Male
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Female
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Aged
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Bone Cements
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Middle Aged
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Thoracic Vertebrae/surgery*
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Lumbar Vertebrae/surgery*
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Retrospective Studies
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Spinal Fractures/surgery*
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Osteoporotic Fractures/surgery*
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Case-Control Studies
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Bone Nails
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Pedicle Screws
5.Clinical implication of post-angioplasty quantitative flow ratio in the patients with coronary artery de novo lesions underwent drug-coated balloons treatment.
Yun-Hui ZHU ; Xu-Lin HONG ; Tian-Li HU ; Qian-Qian BIAN ; Yu-Fei CHEN ; Tian-Ping ZHOU ; Jing LI ; Guo-Sheng FU ; Wen-Bin ZHANG
Journal of Geriatric Cardiology 2025;22(3):332-343
BACKGROUND:
Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions.
METHODS:
Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization.
RESULTS:
A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026).
CONCLUSIONS
In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.
6.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.
7.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
8.Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
Run-min MAO ; Hai-xia ZHAO ; Hai-li DUAN ; Zi-hui GAO ; Ya-nan QU ; Guo-qing FU ; Jian-min MAO ; Jian-ming SUN ; Chang-cheng ZHANG
Chinese Pharmacological Bulletin 2025;41(11):2134-2142
Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.
9.Study on the effectiveness and safety of a novel intravascular shock wave balloon for pre-treatment of severe coronary artery calcification lesions
Rui-tao ZHANG ; Zhen-yu TIAN ; Yong ZENG ; Guo-sheng FU ; Li XU ; Jian LIU ; Jian-ping LI ; Zhi-hui ZHANG ; Xin-qun HU ; Xiang CHENG ; Wen LU ; Ming CUI ; Yi-da TANG
Chinese Journal of Interventional Cardiology 2025;33(2):61-70
Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30%and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P<0.001],the degree of stenosis was significantly reduced[(13.24±6.60)%vs.(65.18±10.59)%,P<0.001].Procedural success was achieved in 100%of cases,and device success was 98.8%.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P<0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P<0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P<0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P<0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.
10.Glutamine signaling specifically activates c-Myc and Mcl-1 to facilitate cancer cell proliferation and survival.
Meng WANG ; Fu-Shen GUO ; Dai-Sen HOU ; Hui-Lu ZHANG ; Xiang-Tian CHEN ; Yan-Xin SHEN ; Zi-Fan GUO ; Zhi-Fang ZHENG ; Yu-Peng HU ; Pei-Zhun DU ; Chen-Ji WANG ; Yan LIN ; Yi-Yuan YUAN ; Shi-Min ZHAO ; Wei XU
Protein & Cell 2025;16(11):968-984
Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism*
;
Myeloid Cell Leukemia Sequence 1 Protein/genetics*
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Humans
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Proto-Oncogene Proteins c-myc/genetics*
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Cell Proliferation
;
Signal Transduction
;
Neoplasms/pathology*
;
F-Box-WD Repeat-Containing Protein 7/genetics*
;
Cell Survival
;
Cell Line, Tumor
;
Apoptosis


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