1.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
2.The jujube core-shaped tissue resection technique in alar reduction
Lehao WU ; Yihao XU ; Huan WANG ; Ruobing ZHENG ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Shan ZHU ; Fei FAN ; Jianjun YOU
Chinese Journal of Plastic Surgery 2024;40(1):88-93
Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.
3.The jujube core-shaped tissue resection technique in alar reduction
Lehao WU ; Yihao XU ; Huan WANG ; Ruobing ZHENG ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Shan ZHU ; Fei FAN ; Jianjun YOU
Chinese Journal of Plastic Surgery 2024;40(1):88-93
Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.
4.Research progress in aging rodent models
Xuechan LI ; Le HAN ; Xuewen WANG ; Lijun LIU ; Jianjun WU ; Jing WANG
Acta Laboratorium Animalis Scientia Sinica 2023;31(12):1605-1609
Aging is a process of degenerative change that occurs as a result of time-related accumulation,associated with age-related diseases.Understanding the causes and mechanisms of aging and finding drugs that can effectively delay aging and prevent and cure age-related diseases currently present a great challenge for humans.Aging animal models thus represent an important tool in aging research,and various aging animal models have been created using different aging mechanisms.These different models having specific advantages and disadvantages,making them suitable for different research purposes.This review considers aging rodent models to provide information for aging research.
5.Application of nasal septum extension graft drilling technique in rib-based rhinoplasty
Yihao XU ; Jianjun YOU ; Huan WANG ; Ruobing ZHENG ; Lehao WU ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Fei FAN
Chinese Journal of Plastic Surgery 2023;39(10):1100-1105
Objective:To investigate the clinical application of a cartilage graft fixation method in the context of rib-based rhinoplasty.Methods:The clinical data of patients who underwent costal cartilage based rhinoplasty in the Center of Rhinoplasty and Nasal Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2020 to January 2022 were retrospectively analyzed. A 20 ml syringe needle was used to drill several micropores about 1 mm in diameter on the surface of the cartilage grafts prior to its placement. "septal extension grafts with micropores" were prepared, and the preparation of the remaining grafts was conventional.Results:A total of 30 female patients aged 21-45 years, with an average age of 36 years underwent primary or repaired autogenous costal cartilage rhinoplasty without severe damage to the nasal septum cartilage (at least retention of L-shaped scaffolds larger than 10 mm) were enrolled. All operations were successful, the cartilage scaffold was stable and durable. There were no serious complications such as infection, septal hematoma and cartilage exposure. Postoperative patients were followed up for a duration of 6-24 months. Two out of 30 patients were not satisfied with the postoperative appearance. During the revision surgery, the septal perichondrium was separated, mucosal tissue had grown into the bilateral holes which further verified of the feasibility of drilling. The other patients were satisfactied with the results.Conclusion:Nasal septum extension graft based on drilling technique is beneficial to maintain the long-term stability of cartilage scaffold after comprehensive costal cartilage nasal surgery, which justifies its application in comprehensive nasal plastic surgery.
6.Application of nasal septum extension graft drilling technique in rib-based rhinoplasty
Yihao XU ; Jianjun YOU ; Huan WANG ; Ruobing ZHENG ; Lehao WU ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Fei FAN
Chinese Journal of Plastic Surgery 2023;39(10):1100-1105
Objective:To investigate the clinical application of a cartilage graft fixation method in the context of rib-based rhinoplasty.Methods:The clinical data of patients who underwent costal cartilage based rhinoplasty in the Center of Rhinoplasty and Nasal Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2020 to January 2022 were retrospectively analyzed. A 20 ml syringe needle was used to drill several micropores about 1 mm in diameter on the surface of the cartilage grafts prior to its placement. "septal extension grafts with micropores" were prepared, and the preparation of the remaining grafts was conventional.Results:A total of 30 female patients aged 21-45 years, with an average age of 36 years underwent primary or repaired autogenous costal cartilage rhinoplasty without severe damage to the nasal septum cartilage (at least retention of L-shaped scaffolds larger than 10 mm) were enrolled. All operations were successful, the cartilage scaffold was stable and durable. There were no serious complications such as infection, septal hematoma and cartilage exposure. Postoperative patients were followed up for a duration of 6-24 months. Two out of 30 patients were not satisfied with the postoperative appearance. During the revision surgery, the septal perichondrium was separated, mucosal tissue had grown into the bilateral holes which further verified of the feasibility of drilling. The other patients were satisfactied with the results.Conclusion:Nasal septum extension graft based on drilling technique is beneficial to maintain the long-term stability of cartilage scaffold after comprehensive costal cartilage nasal surgery, which justifies its application in comprehensive nasal plastic surgery.
7.Open osteotomy in rhinoplasty
Lehao WU ; Jianjun YOU ; Huan WANG ; Yihao XU ; Ruobing ZHENG ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Fei FAN
Chinese Journal of Plastic Surgery 2022;38(3):321-326
Objective:To introduce a new method of lateral nasal osteotomy. The key of this method is to fully dissect the tissue around the piriform foramen to achieve nasal osteotomy under direct vision. The osteotomy line in the whole process can be seen, which provides a more reliable control for the degree of osteotomy during the operation, and also makes the postoperative outcome more predictable.Methods:Patients whom were treated with open external osteotomy combined with autologous costal cartilage implantation for augmentation rhinoplasty (with 24 cases of hump nose correction) from October 2018 to October 2020. During the surgery, the whole nasal dorsum was exposed, the superior lateral cartilage was separated from the nasal septum, and the whole process was carried out through the mucosa from the intranasal approach under direct view. The osteotomy line was evaluated at the same time.Results:A total of 33 female patients were retrospectively analyzed. All the operations were successful, and the local swelling occurred after operation. The follow-up time was 3-18 months. After 3 months, the nasal contour and dorsal curves were smooth. Severe infections, major injuries like nasolacrimal duct, lacrimal sac, medial canthus ligament, nerve branches were not noticed in all patients. During the long-term follow-up, two patients exhibited slightly widened nasal bone, but did not require surgical intervention. The shape of nose was greatly improved. Patients were satisfied with the result . The subjective evaluation had "very satisfactory" in 24 cases (72.7%) and "satisfactory" in 9 cases (27.3%). The IGAIS evaluation were also positive: the average score of 33 patients was 1.26±0.34, including 30 cases (90.9%) scoring 1 point and 3 cases (9.1%) scoring 2 points.Conclusions:The open osteotomy technique has better control than that of conventional blind operation. It is more reliable, safer for the surgeons who are new to rhinoplasty and the experienced ones.
8.Three-dimensional digital technique-assisted clinical study of subalar change after rhinoplasty with costal cartilage
Le TIAN ; Jianjun YOU ; Lehao WU ; Huan WANG ; Binghang LI ; Yihao XU ; Ruobing ZHENG ; Xulong ZHANG ; Junsheng GUO ; Fei FAN
Chinese Journal of Plastic Surgery 2022;38(7):737-743
Objective:To investigate subalar change after rhinoplasty with costal cartilage.Methods:A retrospective study was performed on patients who received cartilaginous rhinoplasty at the Rhinoplasty Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences from May 2019 to August 2020. The facial three-dimensional(3D) and CT scanning data of young female cases was analyzed. Pre-operative and more than 6 months follow-up data was matched. The 3D facial coordinate system was established. Preoperative and postoperative location of the subnasale and the lateral point of nasal-facial junction, the angle between endocanthion-alare and coronal plane and the nasolabial angle were analyzed with paired samples t-test. The volume of subalar area was analyzed with one-sample t-test. Results:Eighteen female cases aged (27.30±4.41) years were enrolled in the study with (10.61±3.53) months follow-up. One case (5.6%) suffered from nostril asymmetry one month after the surgery. The subnasale moved forward from (74.30±1.97) mm to (77.67±2.37) mm [average difference (3.36±0.96) mm]. The lateral point of nasal-facial junction moved forward from (65.51±2.45) mm to (68.05±2.52) mm [average difference (2.53±1.50) mm]. Nasolabial angle was (88.79±11.21) degree preoperatively and (101.37±5.53) degree postoperatively [average difference (12.57±7.57) degree]. Angle between endocanthion-alare and coronal plane increased from (9.01±3.24) degree to (12.73±3.27) degree [average difference (3.72±2.22) degree]. The differences between pre- and post-operative data were statistically significant ( P<0.01). The volume of subalar area increased by (282.59±103.22) mm 3. The difference was statistically significant ( P<0.01). Conclusions:Rhinoplasty with costal cartilage could make subalar area move forward.
9.Effect of propofol on proliferation, invasion and migration of human melanoma cells and role of COX-2/PGE2/MMP signaling pathway
Hua WEI ; Xinhui DU ; Huaping ZHAO ; Le ZHANG ; Yanqiu AI ; Jianjun YANG
Chinese Journal of Anesthesiology 2022;42(5):551-555
Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.
10.Efficacy of remimazolam combined with alfentanil for gastroscopy in frail elderly patients
Hua WEI ; Le ZHANG ; Lu LI ; Yunqi LYU ; Yanqiu AI ; Jianjun YANG
Chinese Journal of Anesthesiology 2022;42(6):708-711
Objective:To evaluate the efficacy of remimazolam combined with alfentanil for gastroscopy in frail elderly patients.Methods:Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ elderly patients, aged 65-85 yr, with body mass index of 18-30 kg/m 2, of Clinical Frailty Scale score≥5, scheduled for elective painless gastroscopy, were divided into 2 groups ( n=30 each) using a random number table method: remimazolam combined with alfentanil group (group R) and propofol combined with remifentanil group (group P). A combination of alfentanil 10 μg/kg and remimazolam 0.2 mg/kg was intravenously injected until loss of consciousness in group R. Remifentanil 0.5 μg/kg combined with propofol 1.0-2.0 mg/kg was intravenously injected until loss of consciousness in group P. According to the intraoperative conditions, 1/4 of the initial dose of remimazolam was intravenously injected in group R, and 1/4 of the initial dose of propofol was intravenously injected in group P. The time for gastroscopy, requirement for additional remimazolam or propofol, onset time of anesthesia, emergence time and time of post-anesthesia care unit stay were recorded.Physician′s satisfaction scores, patient′s satisfaction scores and Verbal Pain Scale scores were recorded.The occurrence of injection pain, respiratory depression, bradycardia, hypotension and nausea and vomit was recorded. Results:There was no significant difference in the requirement for additional remimazolam or propofol, onset time of anesthesia, time for gastroscopy, physician′s satisfaction scores, and patient′s satisfaction scores, Verbal Pain Scale scores and incidence of nausea and vomit between two groups ( P>0.05). Compared with P group, the emergence time and time of post-anesthesia care unit stay were significantly shortened, and the incidence of injection pain (0 vs.33%), respiratory depression (0 vs.20%), hypotension (3% vs.23%) and bradycardia (3% vs.23%) was decreased in R group ( P<0.05). Conclusions:Remimazolam combined with alfentanil is safe and effective, with rapid recovery from anesthesia, and provides better efficacy than the combination of propofol and remifentanil when used for gastroscopy in frail elderly patients.

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