1.Alpha-ketoglutarate engineered small extracellular vesicles delay skin aging
Zhijing WU ; Jiali LI ; Jiaxin ZHANG ; Tangrong WANG ; Yuzhou ZHENG ; Zixuan SUN
Chinese Journal of Tissue Engineering Research 2026;30(1):120-129
BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.
2.Alpha-ketoglutarate engineered small extracellular vesicles delay skin aging
Zhijing WU ; Jiali LI ; Jiaxin ZHANG ; Tangrong WANG ; Yuzhou ZHENG ; Zixuan SUN
Chinese Journal of Tissue Engineering Research 2026;30(1):120-129
BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.
3.Application of elbow skin fold extension line in extreme elbow flexion in ulnar Kirschner wire insertion of extended supracondylar humeral fractures in children.
Xu LIU ; Wei WU ; Yuzhou SHAN ; Guanghui YANG ; Ming CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):70-74
OBJECTIVE:
To discuss the elbow skin fold extension line in Kirschner wire internal fixation of extended supracondylar humeral fractures in children.
METHODS:
The clinical data of 58 children with extended supracondylar fractures of the humerus who met the selection criteria between August 2021 and July 2024 were retrospectively analyzed. In 28 cases, needle placement of medial epicondyle of humerus was performed with the assistance of the elbow skin fold extension line (study group), and 30 cases were assisted by routine touch of the medial epicondyle of the humerus (control group). There was no significant difference in baseline data such as gender, age, side, cause of injury, Gartland type, Kirschner wire configuration, and time from injury to operation between the two groups ( P>0.05). The closed reduction rate, total operation time, time of medial humeral condyle pin placement, fluoroscopy times during medial pin placement, rate of one-time determination of medial entry point, ulnar nerve injury incidence, and fracture healing time were recorded and compared between the two groups. At the same time, the closed reduction rate of patients with the time from injury to operation ≤24 hours and >24 hours was compared. The elbow function was evaluated by Mayo elbow function score.
RESULTS:
The closed reduction rate of the study group was significantly higher than that of the control group ( P<0.05). Among all patients, the closed reduction rate of patients with the time from injury to operation ≤24 hours [73.3% (22/30)] was significantly higher than that of patients >24 hours [42.9% (12/28)] ( χ 2=5.545, P=0.019). The total operation time, medial needle placement time, and fluoroscopy times in the study group were significantly less than those in the control group, and the one-time determination rate of medial needle entry point in the study group was significantly higher than that in the control group ( P<0.05). There were 4 cases of ulnar nerve injury in the control group, and no ulnar nerve injury in the study group, but there was no significant difference in the incidence of ulnar nerve injury between the two groups ( P>0.05). All patients were followed up 6-12 months (mean, 8 months). There was no bone nonunion in both groups, and the fracture healing time of the study group was significantly shorter than that of the control group ( P<0.05). Volkmann ischemic contracture, heterotopic ossification, myositis ossificans, and premature epiphyseal closure were not observed after operation. No complications such as loosening or fracture of Kirschner wire occurred. At last follow-up, the Mayo elbow joint function score was used to evaluate function, and there was no significant difference between the two groups ( P>0.05).
CONCLUSION
In the treatment of extended supracondylar fractures of the humerus in children, the elbow skin fold extension line can help to quickly locate the medial epicondyle of the humerus, quickly insert Kirschner wire, and reduce the operation time and trauma.
Humans
;
Humeral Fractures/surgery*
;
Bone Wires
;
Male
;
Female
;
Fracture Fixation, Internal/instrumentation*
;
Retrospective Studies
;
Child
;
Elbow Joint/physiopathology*
;
Child, Preschool
;
Treatment Outcome
;
Fracture Healing
;
Ulnar Nerve/injuries*
;
Adolescent
;
Range of Motion, Articular
4.Effects and mechanism of ethanol extract of Angelica sinensis(Oliv.)Diels on cell proliferation inhibition and apoptosis induction in B16-F10 melanoma cells
Jiajie KE ; Yuzhou SHEN ; Yaping XU ; Yupei CHEN ; Peiyuan CHEN ; Hongtan WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(1):51-60
AIM:To explore the effect and mecha-nism of ethanol extract of Angelica sinensis(Oliv.)Diels(EEA)on cell proliferation and apoptosis in B16-F10 melanoma cells.METHODS:Cell viability was analyzed by MTT method.Cell proliferation was detected by colony formation assay.The invert-ed microscope was used to observe the changes of cell growth confluence and morphology.Hoechst 33342 staining was used to detect cell apoptosis.Flow cytometry(FCM)was used to detect cell cycle and apoptosis.Transmission electron microscopy(TEM)was used to observe the changes of cell mi-tochondrial structure.Western blot was used to de-tect the expression levels of cell cycle,apoptosis,mitochondrial biogenesis,and mitochondrial dy-namics-related proteins.RESULTS:Compared with the blank control group,the cell viability of B16-F10 melanoma cells was reduced after EEA(10-400μg/mL)treatment for 24 h and 48 h,respectively(P<0.05,P<0.01).The decreased cell growth conflu-ence,morphological changes such as shrinkage,rounding,and reduction in the volume,and apop-totic morphologic changes such as chromatin con-densation were observed after EEA(100 μg/mL and 200 μg/mL)treatment for 24 h.The number of cell clones was decreased after EEA(10-200 μg/mL)treatment for 14 d(P<0.01).The morphology of mitochondria became more round and shorter,and the inner mitochondrial matrices were either damaged or absent after 200 μg/mL EEA treatment for 24 h.The ratio of cells in G0/G1 phase and the early apoptosis rate of cells were higher than those of the blank control group(P<0.01)after EEA(20-200 μg/mL)treatment for 24 h.Western blot re-sults showed that compared with the blank control group,the protein expression levels of cleaved cas-pase-9,Bax,DRP1,and FIS1 were up-regulated(P<0.05,P<0.01),and the protein expression levels of cyclin D1,cyclin E,CDK2,CDK4,Bcl-2,Bad,Bcl-XL,SIRT1,PGC-1α,NRF1,TFAM,MFN2,and OPA1 were down-regulated(P<0.05,P<0.01).CONCLUSION:EEA has an inhibitory effect on the proliferation of B16-F10 melanoma cells,which may be related to the induction of G1/S cell cycle arrest and mito-chondrial apoptotic pathway,and the disruption of mitochondrial biogenesis and mitochondrial dy-namics.
5.Biomechanical Mechanism Discussion of Intervertebral Disc Degeneration on Spinal Stability Based on the Theory of"Muscle and Bone Imbalance,Putting Muscle First"
Yadong WU ; Zhiguo ZHANG ; Jing LI ; Xiaoyan QI ; Yuzhou LU ; Nianhu LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2810-2816
The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".
6.Biomechanical Mechanism Discussion of Intervertebral Disc Degeneration on Spinal Stability Based on the Theory of"Muscle and Bone Imbalance,Putting Muscle First"
Yadong WU ; Zhiguo ZHANG ; Jing LI ; Xiaoyan QI ; Yuzhou LU ; Nianhu LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2810-2816
The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".
7.Effects and mechanism of ethanol extract of Angelica sinensis(Oliv.)Diels on cell proliferation inhibition and apoptosis induction in B16-F10 melanoma cells
Jiajie KE ; Yuzhou SHEN ; Yaping XU ; Yupei CHEN ; Peiyuan CHEN ; Hongtan WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(1):51-60
AIM:To explore the effect and mecha-nism of ethanol extract of Angelica sinensis(Oliv.)Diels(EEA)on cell proliferation and apoptosis in B16-F10 melanoma cells.METHODS:Cell viability was analyzed by MTT method.Cell proliferation was detected by colony formation assay.The invert-ed microscope was used to observe the changes of cell growth confluence and morphology.Hoechst 33342 staining was used to detect cell apoptosis.Flow cytometry(FCM)was used to detect cell cycle and apoptosis.Transmission electron microscopy(TEM)was used to observe the changes of cell mi-tochondrial structure.Western blot was used to de-tect the expression levels of cell cycle,apoptosis,mitochondrial biogenesis,and mitochondrial dy-namics-related proteins.RESULTS:Compared with the blank control group,the cell viability of B16-F10 melanoma cells was reduced after EEA(10-400μg/mL)treatment for 24 h and 48 h,respectively(P<0.05,P<0.01).The decreased cell growth conflu-ence,morphological changes such as shrinkage,rounding,and reduction in the volume,and apop-totic morphologic changes such as chromatin con-densation were observed after EEA(100 μg/mL and 200 μg/mL)treatment for 24 h.The number of cell clones was decreased after EEA(10-200 μg/mL)treatment for 14 d(P<0.01).The morphology of mitochondria became more round and shorter,and the inner mitochondrial matrices were either damaged or absent after 200 μg/mL EEA treatment for 24 h.The ratio of cells in G0/G1 phase and the early apoptosis rate of cells were higher than those of the blank control group(P<0.01)after EEA(20-200 μg/mL)treatment for 24 h.Western blot re-sults showed that compared with the blank control group,the protein expression levels of cleaved cas-pase-9,Bax,DRP1,and FIS1 were up-regulated(P<0.05,P<0.01),and the protein expression levels of cyclin D1,cyclin E,CDK2,CDK4,Bcl-2,Bad,Bcl-XL,SIRT1,PGC-1α,NRF1,TFAM,MFN2,and OPA1 were down-regulated(P<0.05,P<0.01).CONCLUSION:EEA has an inhibitory effect on the proliferation of B16-F10 melanoma cells,which may be related to the induction of G1/S cell cycle arrest and mito-chondrial apoptotic pathway,and the disruption of mitochondrial biogenesis and mitochondrial dy-namics.
8.Correlation of triglyceride-glucose index with unfavorable outcomes following moderate-to-severe traumatic brain injury
Cheng CAO ; Haicheng XU ; Jiachen WANG ; Hongjie ZHAO ; Yuan SHI ; Yuzhou CHEN ; Wei WU ; Heng GAO
Chinese Journal of Trauma 2024;40(2):118-126
Objective:To investigate the correlation between triglyceride-glucose (TyG) index on admission and unfavorable outcomes of patients with moderate-to-severe traumatic brain injury (msTBI) at 6 months postinjury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 277 patients with msTBI admitted to Affiliated Jiangyin Hospital of Nantong University from January 2019 to December 2022, including 208 males and 69 females, aged 18-88 years [(57.0±15.1)years]. Glasgow Coma Scale (GCS) scores on admission were 3-8 points in 168 patients and 9-12 points in 109. According to the Glasgow Outcome Scale-Extended (GOSE) assessment at 6 months after injury, there were 121 patients with unfavorable outcomes (GOSE≤4 points) and 156 with favorable outcomes (GOSE≥5 points). The following indicators of the patients were recorded, including gender, age, history of diabetes, cause of injury, admission GCS, GCS motor score (GCSM), pupillary light reflex, worst Marshall CT classification within the first 24 hours after admission, admission TyG index, Mean Amplitude of Glycemic Excursions (MAGE) within 24 hours after admission, GCSM decline≥2 points within 72 hours after admission, craniotomy or not after admission, and prognosis, etc. TyG index served as the exposure variable focused in this study, which was calculated with fasting triglycerides and fasting blood glucose within 24 hours after admission. The 6-month prognosis of the patients was designated as the outcome variable of the study. After the patients were divided into different groups according to the three quantiles of the TyG index and unfavorable or favorable outcomes, the univariate analysis was conducted on watch variables, and variables with statistically significant differences were included in directed acyclic graphs (DAGs) for further identification of confounding variables. Factors which were found with no statistical significance in the univariate analysis but might affect insulin resistance after injury according to the authors′ previous researches were also included in the DAGs analysis. Three Logistic regression models were designed (Model 1 without correction, Model 2 with core variables of International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) corrected, and Model 3 with confounding variables screened by DAGs corrected) to analyze whether the TyG index was an independent risk factor for the prognosis of msTBI patients. The optimal Logistic regression model was selected and then restricted cubic spline (RCS) was employed to investigate the relationship between the TyG index and the unfavorable outcomes.Results:The univariate analysis suggested that there were significant differences in gender, history of diabetes, MAGE, GCSM decline, and prognosis among the three quantiles of the TyG index ( P<0.05 or 0.01). Significant differences in age, history of diabetes, GCSM, pupillary light reflex, Marshall CT classification, TyG index, MAGE and GCSM decline were observed between unfavorable and favorable outcome groups ( P<0.05 or 0.01). The results of Logistic regression analysis that identified the confounding variables that influenced the correlation between the TyG index and unfavorable prognosis with DAGs suggested that a high TyG index level was significantly correlated with unfavorable outcomes in msTBI patients. Moreover, Model 3 that was corrected with confounding variables screened by DAGs had an optimal goodness-of-fit and adaptability. Model 3-based further RCS analysis indicated that the risk of unfavorable outcomes following msTBI may increase approximately linearly with the increase in TyG index within a certain range (TyG index<9.79). Conclusions:A high TyG index level on admission is the identified as an independent risk factor for unfavorable outcomes of patients with msTBI at 6 months postinjury. As the TyG index level increases, the risk of unfavorable outcomes also rises and may show a linear increasing trend within a certain range (TyG index<9.79).
9.Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial
Pengfei MA ; Sen LI ; Gengze WANG ; Xiaosong JING ; Dayong LIU ; Hao ZHENG ; Chaohui LI ; Yunshuai WANG ; Yinzhong WANG ; Yue WU ; Pengyuan ZHAN ; Wenfei DUAN ; Qingquan LIU ; Tao YANG ; Zuomin LIU ; Qiongyou JING ; Zhanwei DING ; Guangfei CUI ; Zhiqiang LIU ; Ganshu XIA ; Guoxing WANG ; Panpan WANG ; Lei GAO ; Desheng HU ; Junli ZHANG ; Yanghui CAO ; Chenyu LIU ; Zhenyu LI ; Jiachen ZHANG ; Changzheng LI ; Zhi LI ; Yuzhou ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(10):977-985
Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.
10.Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial
Pengfei MA ; Sen LI ; Gengze WANG ; Xiaosong JING ; Dayong LIU ; Hao ZHENG ; Chaohui LI ; Yunshuai WANG ; Yinzhong WANG ; Yue WU ; Pengyuan ZHAN ; Wenfei DUAN ; Qingquan LIU ; Tao YANG ; Zuomin LIU ; Qiongyou JING ; Zhanwei DING ; Guangfei CUI ; Zhiqiang LIU ; Ganshu XIA ; Guoxing WANG ; Panpan WANG ; Lei GAO ; Desheng HU ; Junli ZHANG ; Yanghui CAO ; Chenyu LIU ; Zhenyu LI ; Jiachen ZHANG ; Changzheng LI ; Zhi LI ; Yuzhou ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(10):977-985
Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

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