1.Application of intravenous anesthesia without intubation in transurethral blue laser vaporization of the prostate
Zhenwei FAN ; Zhen HAO ; Guoxiong LIU ; Quan DU ; Yu WANG ; Xiaoliang FU ; Wanglong YUN ; Xiaofeng XU
Journal of Modern Urology 2025;30(6):493-496
Objective: To investigate the safety and feasibility of transurethral blue laser vaporization of the prostate (BVP) under intravenous anesthesia without intubation. Methods: Clinical data of 30 benign prostatic hyperplasia (BPH) (prostate volume <40 mL) patients undergoing BVP under intravenous anesthesia without intubation in our hospital during Jul.and Nov.2024 were retrospectively analyzed.Preoperative and 1-month postoperative international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were compared.The operation time, cumulative blue laser activation time, recovery time, postoperative bladder irrigation time, postoperative catheter indwelling time, postoperative 2-hour visual analog scale (VAS) score and incidence of surgical and anesthetic complications were recorded. Results: All 30 patients successfully completed BVP under intravenous anesthesia without intubation.The operation time was (12.5±5.0) min, cumulative laser activation time (9.8±4.1) min, recovery time (6.8±1.2) min, postoperative bladder irrigation time (11.0±4.6) h, postoperative catheter indwelling time (2.7±1.1) days and postoperative 2-hour VAS score was (3.0±1.3).No cases required conversion to intubated general anesthesia, and no severe perioperative surgical or anesthetic complications occurred.Significant improvements in IPSS, QoL, Qmax, and PVR were observed 1 month postoperatively (P<0.001). Conclusion: BVP under intravenous anesthesia without intubation in the treatment of prostate volume <40 mL BPH is clinically feasible, significantly improving lower urinary tract symptoms without significant surgical or anesthetic complications.
2.The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis
Zhen-Wei LI ; Jing-Yu HOU ; Yu-Ze LIN ; Zhi-Qi ZHANG ; Shang-Yi LIU ; Xiao-Wen LIU ; Kang-Quan SHOU
Progress in Biochemistry and Biophysics 2024;51(7):1576-1588
The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.
3.Determination of 19 components in Microctis Folium from different production areas based on UPLC-MS/MS
Min-you HE ; Li-wei WANG ; Lin LIU ; Po-yu ZHANG ; Jin-quan LAN ; Xin-ya WAN ; Zhen-yu LI ; Xiang-dong CHEN ; Dong-mei SUN
Acta Pharmaceutica Sinica 2024;59(5):1374-1381
The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.
4.Clinical study of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hyper-tension complicated with paroxysmal atrial fibrillation
Yong HOU ; Lian-Fa WANG ; Hong-Tao LU ; Zhen CHEN ; Meng-Xun HUANG ; Chen CHEN ; Bang-Zhu ZHANG ; Quan-Xiu TONG ; Yun-Fei WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(1):40-44
Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)%vs.1.62(3.50)%],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P<0.05 or<0.01).There were no significant difference in LVEDd and LVEF between two groups,P>0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.
5.Liuwei Dihuang Pills-elicited inhibition of MMP-2/MMP-9 via RAGE on tight junction protein of Aβ1-40-injured bEnd.3 cells
Rui DING ; Yong YUAN ; Ya-Quan JIA ; Ai-She GAO ; Zhen-Qiang ZHANG ; Jun-Ying SONG
Chinese Traditional Patent Medicine 2024;46(2):424-430
AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.
6.Use of " short distances and multi-segment" buried guiding suture in the surgery of early descent of prosthesis after augmentation mammoplasty
Wenchao YU ; Zhiyuan JIANG ; Zaihong CHEN ; Xiaobo YOU ; Zhen CAI ; Quan LIU ; Liping DU ; Wei CUI ; Yang SHENG
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(1):42-46
Objective:To introduce a surgical technique of " short distances and multi-segment" buried-guiding suture method and its effects in the surgery of early descent of prosthesis after augmentation mammaplasty.Methods:From August 2019 to January 2022, 15 cases of early descent of prosthesis after augmentation mammaplasty due to axillary approach breast augmentation for micromastia were admitted to the Plastic Surgery Department of Sichuan Provincial People′s Hospital, aged 23-35 years (27.3±3.6) and duration of dislocation from 16 to 35 days (23.8±5.8). There were 12 patients showed unilateral prosthesis drops and 3 patients showed bilateral prosthesis drops. " Short distances and multi-segment" buried-guiding suture method was used to solve the problem, i. e., 2-0 non-absorbable sutures were used to eliminate the lower pole of prosthetic cavity with " short distances and multi-segment" sutures. The distance from the nipple to the midline of the sternum, the distance from the sternotomy to the nipple, the distance from the nipple to the inframammary fold and the distance from the midclavicular point to the inframammary fold were measured bilaterally before and after surgery, and statistical analysis was performed to evaluate the efficacy of the " short distances and multi-segment" buried-guiding suture method for early descent of prosthesis after breast augmentation.Results:All incisions healed by first intention without complications such as hematoma, infection, or scar hyperplasia. 15 patients were followed up for 6-12 months (8.0±1.9). 14 patients were satisfied with the results after surgery, and 1 patient received satisfactory results after secondary surgery. The distance from nipple to inframammary fold was shortened by 0.8-1.4 cm after surgery (1.2±0.2), and the distance from mid-clavicle to inframammary fold was shortened by 1.0-1.6 cm (1.3±0.4), and the differences were statistically significant as compared with the values before surgery ( t=31.17, P<0.05; t=33.78, P<0.05). After surgery, the change in the distance from nipple to sternal was 0.1-0.3 cm (0.16±0.10), and the change in the distance from sternal notch to nipple was 0-0.2 cm (0.12±0.10), and the differences were not statistically significant ( P>0.05). Conclusions:With the advantages of simple operation, little trauma and no additional incision, the " short distance and multi-stage" buried-guiding suture method in the surgery of early descent of prosthesis after augmentation mammaplasty is worthy of clinical application.
7.Endovascular treatment of ruptured internal carotid pseudoaneurysm with bleeding after radiotherapy for nasopharyngeal carcinoma
Quan SHEN ; Qubin ZHENG ; Hang XIE ; Zhen CHI ; Ning HUANG
Journal of Interventional Radiology 2024;33(3):304-308
Objective To discuss the methods,efficacy,and safety of endovascular treatment for ruptured pseudoaneurysm hemorrhage of internal carotid artery(ICA)after radiotherapy for nasopharyngeal carcinoma(NPC).Methods The clinical data of 21 patients with ruptured pseudoaneurysm hemorrhage of ICA after radiotherapy for NPC,who were admitted to the Affiliated Union Hospital,Fujian Medical University of China,were retrospectively analyzed.The patient's surgical strategies were analyzed,the therapeutic results and the clinical and imaging follow-up results were summarized.Of the 21 patients,covered stent implantation was carried out in 8,stent-assisted coil embolization was employed in 6,and direct occlusion of parent artery was adopted in 7.Results Successful endovascular treatment was accomplished in all the 21 patients.Excellent hemostatic effect was obtained immediately after surgery.Aneurysm neck residue was observed in 2 patients,and aneurysm body residue was seen in one patients.Postoperative bleeding recurred in 5 patients,in 4 of them the bleeding stopped after once more occlusion of the parent artery,and one patient developed internal leakage after covered stent implantation and the bleeding stopped after balloon dilation,and this patient died of unknown cause one month later.One patient developed coma after covered stent implantation,CT scan demonstrated subarachnoid hemorrhage and brain swelling,and this patient showed no improvement after treatment and was self-discharged from hospital.ICA occlusion was seen in 3 patients during follow-up period,and 2 patients did not receive a postoperative follow-up visit.In the 19 patients who were followed up,the mRS score was 0 point(n=9),1 point(n=6),2 points(n=2),5 points(n=1),and 6 points(n=1).Conclusion For the ruptured pseudoaneurysm hemorrhage of ICA after radiotherapy for NPC,endovascular treatment is highly safe with reliable efficacy.The covered stent implantation carries good short-term efficacy,but there are also problems such as aneurysm recurrence,internal endoleak,etc.The direct occlusion of parent artery may have more reliable long-term efficacy.(J Intervent Radiol,2024,33:304-308)
8.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
9.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
10.Application of near-infrared autofluorescence probe in intraoperative parathyroid gland identification
Surong HUA ; Junyi GAO ; Zhen CAO ; Huaijin ZHENG ; Hongyu WANG ; Xiaojing NING ; Liyuan FU ; Yang ZHANG ; Yikun WANG ; Ziwen LIU ; Quan LIAO
Chinese Journal of Endocrine Surgery 2024;18(5):675-678
Objective:To explore the use of near-infrared autofluorescence probe (NIRAF-P) and its application in identifying parathyroid glands during surgery.Methods:A total of 68 patients undergoing thyroid surgery at Peking Union Medical College Hospital and Beijing Longfu Hospital between Dec. 2023 and Jun. 2024 were selected. During the operation, the near-infrared parathyroid gland detector was used to identify the parathyroid gland tissue to be tested, and histopathological examination was performed. The positive predictive value and accuracy of the near-infrared parathyroid gland detector were analyzed.Results:A total of 111 parathyroid glands were identified in 68 patients, and the positive predictive value and accuracy of the NIRAF-P were 95.5% and 94.6%, respectively.Conclusions:The NIRAF-P has high accuracy in identifying parathyroid glands. The standardized application of the NIRAF-P can help improve the efficiency of identifying parathyroid glands during surgery.

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