Objective To establish a method for the determination of mercury, methylmercury (MeHg) and ethylmercury (EtHg) in the hair of mercury-exposed individuals using high performance liquid chromatography-atomic fluorescence spectrometry. Methods About 0.20 g of hair was mixed with 5.0 mL of hydrochloric acid to a concentration of 5.00 mol/L. After standing for 12 hours, ultrasonic extraction was carried out for 30 minutes at room temperature. Ammonia solution was added dropwise into 2.0 mL supernatant after centrifuge to adjust the pH to 4-5. The solution was diluted to 10.0 mL with pure water after mixed with 0.2 mL of L-cysteine with a mass concentration of 10.0 g/L. The mobile phase consisted of 5.0% methanol + a mass concentration of 0.06 mol/L ammonium acetate + a 0.1% L-cysteine, and was used for separation by a C₁₈ liquid chromatography column, followed by detection using atomic fluorescence spectrometry after UV digestion. Results The linear relationship of mercury, MeHg and EtHg in human hair was good at mass concentrations of 0.0-10.0 μg/L, with all correlation coefficients >0.999 0. The detection limit of mercury, MeHg and EtHg was 0.008, 0.008, and 0.010 μg/g, respectively. The within- and between- run relative standard deviations of the three forms of mercury were 1.6%-4.3% and 2.0%-5.6%, respectively, and the recovery rates were 94.0%-101.2%. Conclusion This method is simple, with low detection limit, high sensitivity, and good accuracy, and is suitable for the simultaneous determination of mercury, MeHg and EtHg in the hair of mercury-exposed individuals.

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

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.

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.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective:To explore the effects of posterior malleolar fracture fixation on the rotational stability of the ankle joint.Methods:A total of 20 fresh cadaveric specimens of lower limbs were anatomized to measure the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia. One healthy volunteer was selected to construct a finite element model for the intact tibiofibular and ankle joints and finite element models for posterior malleolar fracture with different posterior projection areas. A load of 600 N was vertically applied to the inferior calcaneus along the tibial mechanical axis. The contact area and maximum Von Mises stress of the distal tibial articular surface were analyzed to verify the validity of the model for the intact tibiofibular and ankle joints. In the finite element models for the posterior malleolar fracture (S, 1/2S, 1/4S, 1/8S and 1/16S model groups, with S standing for the complete projection area of the ligament complex on the posterior surface of the tibia), the width increase in the tibiofibular clear space was measured when a vertical load of 600 N and external rotation load of 5 N·m were applied to the ankle joint after the reduction and fixation of posterior malleolar fracture. The cutoff value of the posterior projection area of posterior malleolar fracture that could maintain the rotational stability of the ankle joint was assessed.Results:The measurement results of the cadaveric specimens showed that the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia was relatively large. It was attached to the posterolateral area of the distal tibia with the highest point located at (45.2±5.6)mm from the articular surface. With the increase in the distance from the joint line, the width of the posterior attachment area of the ligament complex was decreased. Results of the finite element analysis showed that in the finite element model for the intact tibiofibular and ankle joints, the tibiotalar joint contact area was 324.02 mm 2 and the maximum Von Mises stress was 4.495 1 MPa with a vertical load of 600 N. In the finite element models for the posterior malleolar fracture, the distal tibiofibular clear spaces of the S, 1/2S, 1/4S and 1/8S model groups increased by less than 2 mm following loading, while it was increased by 3.445 8 mm in the 1/16S model group. The cutoff value of the posterior tibial projection area that could maintain the rotational stability of the ankle joint was 1/8S. Conclusions:The attachment area of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia is large. Both the axial stability and rotational stability of the ankle joint should be considered in the treatment selection for posterior malleolar fracture. Simple posterior malleolar fixation is recommended to restore the rotational stability and axial stability of the ankle joint when tibiofibular syndesmosis is unstable and the cutoff value is larger than or equal to 1/8, while tibiofibular syndesmosis screws must be implanted when tibiofibular syndesmosis is unstable and the cutoff value is less than 1/8.

Objective:A novel anatomic posterior malleolus locking plate for Chinese people was designed, researched, developed, and tested biomechanically.Methods:An anatomic parameter database of posterior malleolus of Chinese people was established by collecting CT images of ankle joints from 100 healthy volunteers in Shanghai Tongji hospital from June 2022 to May 2023. Combined with relevant computer-aided technologies, a novel anatomic posterior malleolus locking plate for Chinese people was designed and produced. In addition, model verification and biomechanical test were carried out on vertical displacements under different fixation modes and different axial loads (500, 1 000, and 1 500 N). Failure loads at a displacement of 2 mm and maximum failure loads at the complete failure of internal fixation were also tested and recorded.Results:Based on the imaging anatomic measurement, the width quartile of posterior malleolus was 19.4, 26.6, 35.0 mm. The 3D reconstruction models of ankle joint CT corresponded to small, medium, and large basic posterior malleolus plates. Height of the screw safety zone was 5.5(5.3, 5.7) mm. The tip-back angle was 153.0°(148.5°, 157.5°) and tip-back height was 20.0(19.7, 20.9) mm. The novel anatomic posterior malleolus locking plate based on tibiofibular and ankle joint CT scan and relevant computer-aided technologies fit well with posterior malleolus of tibia, showing anatomic fitting. Based on the associate biomechanical test, the novel plate fixation had smaller vertical displacements of posterior malleolus fragment under axial loads of 500, 1 000, and 1 500 N compared with the control plate, but greater failure loads when the vertical displacement of the posterior malleolus fragment was 2 mm and greater maximum failure loads at complete failure of the internal fixation. At an axial load of 500 N, the vertical displacements of the posterior malleolus fragment after posterior malleolus fixation with a control plate, a 6-hole anatomical locking plate, and a 5-hole anatomical locking plate were 0.60±0.02, 0.45±0.04, and 0.52±0.04 mm, respectively with significant difference ( F=88.287, P<0.001); at an axial load of 1 000 N, the vertical displacements were 2.22±0.03, 1.10±0.03, and 1.15±0.03 mm for the three fixation modes, respectively, and the difference was statistically significant ( F=10 061.890, P<0.001); At an axial load of 1 500 N, the vertical displacements were 2.81±0.04, 1.50±0.03 and 1.67±0.03 mm for the three fixation modes, respectively with significant difference ( F=9 774.019, P<0.001). When the vertical displacement of the posterior malleolus fragment was 2 mm, the failure loads for the three fixation modes were 0.80(0.73, 0.80)、2.00(1.93, 2.00) and 1.70(1.70, 1.70) kN, respectively with significant differences ( H=54.245, P<0.001). The maximum failure loads at complete failure of the internal fixation for the three fixation modes were 1.90(1.90, 1.98)、4.30(4.30, 4.30) and 3.70(3.63, 3.70) kN, respectively with significant differences ( H=53.863, P<0.001). Conclusions:The novel anatomic posterior malleolus locking plate for Chinese people was well matched to the posterior malleolus with high mechanical strength and good stability, showing a promising future for clinical application.

OBJECTIVE: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. METHODS: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. RESULTS: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. CONCLUSION With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.
Humans ; Female ; Tibia/surgery* ; Finite Element Analysis ; Ankle ; Arthritis ; Fibula/surgery* ; Ankle Joint/surgery*

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.