1.Analysis of gene expression in synovial fluid and blood of patients with knee osteoarthritis of Yang deficiency and blood stasis type.
Hao-Tian HUA ; Zhong-Yi ZHANG ; Zhao-Kai JIN ; Peng-Qiang LOU ; Zhuo MENG ; An-Qi ZHANG ; Yang ZHANG ; Pei-Jian TONG
China Journal of Orthopaedics and Traumatology 2025;38(8):792-799
OBJECTIVE:
To reveal the molecular basis of knee osteoarthritis (KOA) with Yang deficiency and blood stasis syndrome by analyzing the gene expression profiles in synovial fluid and blood of KOA patients with this syndrome.
METHODS:
A total of 80 KOA patients were recruited from October 2022 to June 2024, including 40 cases in the non-Yang deficiency and blood stasis group (27 males and 13 females), with an average age of (61.75±3.45) years old;and 40 cases in the Yang deficiency and blood stasis group (22 males and 18 females), with an average age of (62.00±2.76) years old. The levels of body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), fibrinogen, total cholesterol, and D-dimer were recorded and summarized. Blood and synovial fluid samples from patients were collected for gene expression profile microarray sequencing, and then PCR and immunohistochemistry were used for clinical verification on the patients' synovial fluid and cartilage samples.
RESULTS:
Logistic regression analysis showed that compared with KOA patients with non-Yang deficiency and blood stasis syndrome, those with Yang deficiency and blood stasis syndrome had increased BMI, LDL, fibrinogen, total cholesterol, and D-dimer, and decreased HDL, with a clear correlation between the two groups. There were 562 differential genes in the blood, among which 322 were up-regulated and 240 were down-regulated;755 differential genes were found in the synovial fluid, with 350 up-regulated and 405 down-regulated. KEGG signaling pathway analysis of synovial fluid revealed changes in lipid metabolism-related pathways, including cholesterol metabolism, fatty acid metabolism, and PPARG signaling pathway. Analysis of the involved differential genes identified 6 genes in synovial fluid that were closely related to lipid metabolism, namely LRP1, LPL, ACOT6, TM6SF2, DGKK, and PPARG. Subsequently, PCR and immunohistochemical verification were performed using synovial fluid and cartilage samples, and the results were consistent with those of microarray sequencing.
CONCLUSION
This study explores the clinical and genomic correlation between traditional Chinese medicine syndromes and knee osteoarthritis from the perspective of lipid metabolism, and proves that abnormal lipid metabolism is closely related to KOA with Yang deficiency and blood stasis syndrome from both clinical and basic aspects.
Humans
;
Male
;
Female
;
Middle Aged
;
Synovial Fluid/metabolism*
;
Osteoarthritis, Knee/metabolism*
;
Yang Deficiency/complications*
;
Aged
2.Safety and efficacy of robotic-assisted vs.laparoscopic hepatectomy for the treatment of hepatic hemangiomas
Gaiming JIANG ; Kai ZHENG ; Yukai LI ; Jing LI ; Qiang KANG ; Yang KE ; Yuehua LI
Chinese Journal of General Surgery 2025;34(1):70-78
Background and Aims:Hepatectomy is an important treatment option for hepatic hemangioma,and the approach has gradually shifted from traditional open surgery to laparoscopic and robotic-assisted surgery.However,there is still no consensus on whether robotic assistance provides better treatment outcomes than laparoscopic surgery for hepatic hemangioma.Therefore,this study was performed to evaluate and compare the clinical efficacy and safety of robotic-assisted and laparoscopic hepatectomy for the treatment of hepatic hemangioma.Methods:The clinical data of 184 patients who underwent minimally invasive hepatectomy for hepatic hemangioma in the Department of Hepatobiliary and Pancreatic Surgery,Second Affiliated Hospital of Kunming Medical University,between February 2021 and July 2024 were retrospectively collected.Among them,30 cases were in the robotic group,and 154 cases were in the laparoscopic group.Propensity score matching(PSM)was performed based on baseline data such as patient demographics,tumor characteristics,and surgical resection range,with a 1∶2 matching ratio.Intraoperative and postoperative outcomes were compared between the two groups after matching.Results:After 1∶2 PSM,24 patients were in the robotic group and 48 in the laparoscopic group.Preoperative variables were well balanced between the groups(area under the ROC curve was 0.588).The robotic group had significantly shorter operative time(138 min vs.168 min,P=0.024)and hepatic hilum blocking time(25 min vs.45 min,P<0.001)compared to the laparoscopic group.Postoperative albumin levels on day 1 and day 3 were higher in the robotic group,while transaminase levels on postoperative day 1 and day 3 were lower(all P<0.05).However,the hospitalization cost was higher in the robotic group than that in the laparoscopic group(74 746 yuan vs.49 644 yuan,P<0.001).No significant differences were found between the groups in terms of intraoperative blood loss,intraoperative transfusion rate,open conversion rate,postoperative length of stay,and postoperative complication rates as well as complication severity(all P>0.05).Conclusion:For suitable cases of hepatic hemangioma,robotic-assisted laparoscopic hepatectomy is a safe and feasible treatment option.Compared to traditional laparoscopic surgery,it reduces operative time and hepatic hilum blocking time,and minimizes the impact on postoperative liver function.However,the treatment cost is higher,and selection should be based on the patient's individual needs.
3.Evaluation of a deep learning-driven centerline extraction algorithm for optimizing the diagnosis of the"gray zone"in noninvasive coronary fractional flow reserve
Zi-qiang GUO ; Xi WANG ; Zi-nuan LIU ; Yi-pu DING ; Ran XIN ; Dong-kai SHAN ; Jun GUO ; Yun-dai CHEN ; Jun-jie YANG
Chinese Journal of Interventional Cardiology 2025;33(6):312-318
Objective To evaluate the diagnostic performance of the minimum-cost-path-based CT angiography-derived fractional flow reserve(MCP-FFR)and the deep learning-driven CT angiography-derived fractional flow reserve(DeepCL-FFR),and to particularly explore the potential value of the DeepCL algorithm in improving diagnostic accuracy within the"gray zone."Methods A retrospective analysis was conducted on 151 coronary vessels from 109 patients with coronary artery disease,who were hospitalized at the General Hospital of the People's Liberation Army between January 2020 and June 2021.Pearson correlation and Bland-Altman plots were employed to assess the correlation and agreement of the two CT-FFR methods with invasive FFR.A CT-FFR range of 0.70-0.80 was defined as the diagnostic"gray zone."The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value for detecting hemodynamic abnormalities were calculated and analyzed.The DeLong test was used to compare the areas under the receiver operating characteristic curves(AUC)between the two CT-FFR calculation methods.Results Both CT-FFR methods exhibited a positive correlation with invasive FFR(MCP-FFR:r=0.75,P<0.001;DeepCL-FFR:r=0.86,P<0.001)and showed good agreement(MCP-FFR:mean difference=0.010,P=0.351;DeepCL-FFR:mean difference=-0.003,P=0.772).Both DeepCL-FFR(AUC 0.97,95%CI 0.94-0.99)and MCP-FFR(AUC 0.92,95%CI 0.88-0.97)demonstrated favorable diagnostic performance for detecting hemodynamic abnormalities(P=0.122).In the"gray zone"for hemodynamic abnormality,the diagnostic accuracy of MCP-FFR was 68.8%,whereas DeepCL-FFR increased it to 89.7%.DeepCL-FFR also exhibited superior diagnostic performance(AUC 0.89,95%CI 0.73-0.99)within the"gray zone,"which was significantly higher than that of MCP-FFR(AUC 0.71,95%CI 0.54-0.87)(P<0.001).Conclusions The deep learning-driven coronary centerline extraction algorithm,DeepCL,demonstrates superior diagnostic performance in CT-FFR for detecting hemodynamic abnormalities,particularly by significantly improving diagnostic accuracy in the"gray zone."
4.Preliminary exploration of the efficacy and safety of darolutamide in the treatment of metastatic hormone-sensitive prostate cancer
Zekun XIN ; Shuyu ZHANG ; Yuqiang SHI ; Zhentao LEI ; Kai LE ; Jie XIONG ; Lin YANG ; Shenghan WANG ; Qiang GAO ; Bao ZHANG
Chinese Journal of Urology 2025;46(3):188-191
Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.
5.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.
6.Evaluation of a deep learning-driven centerline extraction algorithm for optimizing the diagnosis of the"gray zone"in noninvasive coronary fractional flow reserve
Zi-qiang GUO ; Xi WANG ; Zi-nuan LIU ; Yi-pu DING ; Ran XIN ; Dong-kai SHAN ; Jun GUO ; Yun-dai CHEN ; Jun-jie YANG
Chinese Journal of Interventional Cardiology 2025;33(6):312-318
Objective To evaluate the diagnostic performance of the minimum-cost-path-based CT angiography-derived fractional flow reserve(MCP-FFR)and the deep learning-driven CT angiography-derived fractional flow reserve(DeepCL-FFR),and to particularly explore the potential value of the DeepCL algorithm in improving diagnostic accuracy within the"gray zone."Methods A retrospective analysis was conducted on 151 coronary vessels from 109 patients with coronary artery disease,who were hospitalized at the General Hospital of the People's Liberation Army between January 2020 and June 2021.Pearson correlation and Bland-Altman plots were employed to assess the correlation and agreement of the two CT-FFR methods with invasive FFR.A CT-FFR range of 0.70-0.80 was defined as the diagnostic"gray zone."The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value for detecting hemodynamic abnormalities were calculated and analyzed.The DeLong test was used to compare the areas under the receiver operating characteristic curves(AUC)between the two CT-FFR calculation methods.Results Both CT-FFR methods exhibited a positive correlation with invasive FFR(MCP-FFR:r=0.75,P<0.001;DeepCL-FFR:r=0.86,P<0.001)and showed good agreement(MCP-FFR:mean difference=0.010,P=0.351;DeepCL-FFR:mean difference=-0.003,P=0.772).Both DeepCL-FFR(AUC 0.97,95%CI 0.94-0.99)and MCP-FFR(AUC 0.92,95%CI 0.88-0.97)demonstrated favorable diagnostic performance for detecting hemodynamic abnormalities(P=0.122).In the"gray zone"for hemodynamic abnormality,the diagnostic accuracy of MCP-FFR was 68.8%,whereas DeepCL-FFR increased it to 89.7%.DeepCL-FFR also exhibited superior diagnostic performance(AUC 0.89,95%CI 0.73-0.99)within the"gray zone,"which was significantly higher than that of MCP-FFR(AUC 0.71,95%CI 0.54-0.87)(P<0.001).Conclusions The deep learning-driven coronary centerline extraction algorithm,DeepCL,demonstrates superior diagnostic performance in CT-FFR for detecting hemodynamic abnormalities,particularly by significantly improving diagnostic accuracy in the"gray zone."
7.Safety and efficacy of robotic-assisted vs.laparoscopic hepatectomy for the treatment of hepatic hemangiomas
Gaiming JIANG ; Kai ZHENG ; Yukai LI ; Jing LI ; Qiang KANG ; Yang KE ; Yuehua LI
Chinese Journal of General Surgery 2025;34(1):70-78
Background and Aims:Hepatectomy is an important treatment option for hepatic hemangioma,and the approach has gradually shifted from traditional open surgery to laparoscopic and robotic-assisted surgery.However,there is still no consensus on whether robotic assistance provides better treatment outcomes than laparoscopic surgery for hepatic hemangioma.Therefore,this study was performed to evaluate and compare the clinical efficacy and safety of robotic-assisted and laparoscopic hepatectomy for the treatment of hepatic hemangioma.Methods:The clinical data of 184 patients who underwent minimally invasive hepatectomy for hepatic hemangioma in the Department of Hepatobiliary and Pancreatic Surgery,Second Affiliated Hospital of Kunming Medical University,between February 2021 and July 2024 were retrospectively collected.Among them,30 cases were in the robotic group,and 154 cases were in the laparoscopic group.Propensity score matching(PSM)was performed based on baseline data such as patient demographics,tumor characteristics,and surgical resection range,with a 1∶2 matching ratio.Intraoperative and postoperative outcomes were compared between the two groups after matching.Results:After 1∶2 PSM,24 patients were in the robotic group and 48 in the laparoscopic group.Preoperative variables were well balanced between the groups(area under the ROC curve was 0.588).The robotic group had significantly shorter operative time(138 min vs.168 min,P=0.024)and hepatic hilum blocking time(25 min vs.45 min,P<0.001)compared to the laparoscopic group.Postoperative albumin levels on day 1 and day 3 were higher in the robotic group,while transaminase levels on postoperative day 1 and day 3 were lower(all P<0.05).However,the hospitalization cost was higher in the robotic group than that in the laparoscopic group(74 746 yuan vs.49 644 yuan,P<0.001).No significant differences were found between the groups in terms of intraoperative blood loss,intraoperative transfusion rate,open conversion rate,postoperative length of stay,and postoperative complication rates as well as complication severity(all P>0.05).Conclusion:For suitable cases of hepatic hemangioma,robotic-assisted laparoscopic hepatectomy is a safe and feasible treatment option.Compared to traditional laparoscopic surgery,it reduces operative time and hepatic hilum blocking time,and minimizes the impact on postoperative liver function.However,the treatment cost is higher,and selection should be based on the patient's individual needs.
8.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.
9.Preliminary exploration of the efficacy and safety of darolutamide in the treatment of metastatic hormone-sensitive prostate cancer
Zekun XIN ; Shuyu ZHANG ; Yuqiang SHI ; Zhentao LEI ; Kai LE ; Jie XIONG ; Lin YANG ; Shenghan WANG ; Qiang GAO ; Bao ZHANG
Chinese Journal of Urology 2025;46(3):188-191
Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.
10.Questionnaire Survey on General Medicine and Pre-hospital First Aid Knowledge Among People in Ludian County,Yunnan Province
Weiyu ZHOU ; Dexing YANG ; Qiang WANG ; Zhenfang WANG ; Kai FU ; Jiefu TANG ; Shengzhe LIU ; Ying LUAN ; Min LI ; Rong LIU
Journal of Kunming Medical University 2024;45(3):118-126
Objective To explore the public's cognition and attitude towards general medicine,general practitioners,and pre-hospital first-aid knowledge in Ludian County,Yunnan Province,to find out the training and learning methods that are more acceptable to the public for this kind of related knowledge,and to propose targeted solutions.Methods A complete random sampling survey was conducted among the nucleic acid collection office at the gate of the vegetable market from October 15,2022,to December 30,2022,and the outpatient clinic of Wenping Street Health Center from January 1,2023,to February 28,2023,by using electronic questionnaire and paper questionnaire.Results Nearly 50%of the people in Ludian County of Yunnan Province lack the knowledge of general medicine and pre-hospital emergency care,especially the knowledge of electrical defibrillation.People with higher education and the medical profession have a higher understanding of general medicine,and people with a higher understanding of general medicine are more willing to participate in pre-hospital emergency care.The average Ridit value is:very familiar with general medicine(0.774)>Knowledge of some general practices(0.565)>Never heard of general practice(0.400).The higher education level and the more comprehensive understanding of general medicine had a positive impact on participation in pre-hospital emergency care,with B values of 0.624 and 0.619,OR 95%CI of 1.867(1.544~2.257)and 1.857(1.298~2.657),respectively.Taking medical staff as a reference,the B value of medical students was = 0.942,P = 0.234,the difference was not significant,and the B value of non-medical professional population was all less than 0,the effect is negative.In addition,most people have a positive attitude towards learning pre-hospital first aid,and more than 70%of people are willing to learn and train related knowledge of pre-hospital first aid.Conclusions People in urban areas of Ludian County,Yunnan Province have poor understanding of general practice,low recognition of general practitioners,low demand for general practitioners,and lack of awareness of the importance of pre-hospital emergency treatment.Because of the cognitive differences among different groups,it is necessary to conduct specific training for different groups.

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