Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement 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 rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To investigate the prevalence and risk factors of sarcopenia in patients following radical gastrectomy with the aim of guiding clinical decisions.Methods:This was a retrospective observational study of data of patients who had undergone radical gastrectomy between June 2021 and June 2022 at the Department of General Surgery, First Medical Center of Chinese PLA General Hospital. Participants were reviewed 9-12 months after surgery. Inclusion criteria were as follows: (1) radical gastrectomy with a postoperative pathological diagnosis of primary gastric cancer; (2) no invasion of neighboring organs, peritoneal dissemination, or distant metastasis confirmed intra- or postoperatively; (3) availability of complete clinical data, including abdominal enhanced computed tomography and pertinent blood laboratory tests 9-12 after surgery. Exclusion criteria were as follows: (1) age <18 years; (2) presence of gastric stump cancer or previous gastrectomy; (3) history of or current other primary tumors within the past 5 years; (4) preoperative diagnosis of sarcopenia (skeletal muscle index [SMI) ≤52.4 cm2/m2 for men, SMI ≤38.5 cm2/m2 for women). The primary focus of the study was to investigate development of postoperative sarcopenia in the study cohort. Univariate and multivariate logistic regression were used to identify the factors associated with development of sarcopenia after radical gastrectomy.Results:The study cohort comprised 373 patients of average age of 57.1±12.3 years, comprising 292 (78.3%) men and 81 (21.7%) women. Postoperative sarcopenia was detected in 81 (21.7%) patients in the entire cohort. The SMI for the entire group was (41.79±7.70) cm 2/m 2: (46.40±5.03) cm 2/m 2 for men and (33.52±3.63) cm 2/m 2 for women. According to multivariate logistic regression analysis, age ≥60 years (OR=2.170, 95%CI: 1.175-4.007, P=0.013), high literacy (OR=2.512, 95%CI: 1.238-5.093, P=0.011), poor exercise habits (OR=3.263, 95%CI: 1.648-6.458, P=0.001), development of hypoproteinemia (OR=2.312, 95%CI: 1.088–4.913, P=0.029), development of hypertension (OR=2.169, 95%CI: 1.180-3.984, P=0.013), and total gastrectomy (OR=2.444, 95%CI:1.214-4.013, P=0.012) were independent risk factors for postoperative sarcopenia in post-gastrectomy patients who had had gastric cancer ( P<0.05). Conclusion:Development of sarcopenia following radical gastrectomy demands attention. Older age, higher education, poor exercise habits, hypoproteinemia, hypertension, and total gastrectomy are risk factors for its development post-radical gastrectomy.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To investigate the prevalence and risk factors of sarcopenia in patients following radical gastrectomy with the aim of guiding clinical decisions.Methods:This was a retrospective observational study of data of patients who had undergone radical gastrectomy between June 2021 and June 2022 at the Department of General Surgery, First Medical Center of Chinese PLA General Hospital. Participants were reviewed 9-12 months after surgery. Inclusion criteria were as follows: (1) radical gastrectomy with a postoperative pathological diagnosis of primary gastric cancer; (2) no invasion of neighboring organs, peritoneal dissemination, or distant metastasis confirmed intra- or postoperatively; (3) availability of complete clinical data, including abdominal enhanced computed tomography and pertinent blood laboratory tests 9-12 after surgery. Exclusion criteria were as follows: (1) age <18 years; (2) presence of gastric stump cancer or previous gastrectomy; (3) history of or current other primary tumors within the past 5 years; (4) preoperative diagnosis of sarcopenia (skeletal muscle index [SMI) ≤52.4 cm2/m2 for men, SMI ≤38.5 cm2/m2 for women). The primary focus of the study was to investigate development of postoperative sarcopenia in the study cohort. Univariate and multivariate logistic regression were used to identify the factors associated with development of sarcopenia after radical gastrectomy.Results:The study cohort comprised 373 patients of average age of 57.1±12.3 years, comprising 292 (78.3%) men and 81 (21.7%) women. Postoperative sarcopenia was detected in 81 (21.7%) patients in the entire cohort. The SMI for the entire group was (41.79±7.70) cm 2/m 2: (46.40±5.03) cm 2/m 2 for men and (33.52±3.63) cm 2/m 2 for women. According to multivariate logistic regression analysis, age ≥60 years (OR=2.170, 95%CI: 1.175-4.007, P=0.013), high literacy (OR=2.512, 95%CI: 1.238-5.093, P=0.011), poor exercise habits (OR=3.263, 95%CI: 1.648-6.458, P=0.001), development of hypoproteinemia (OR=2.312, 95%CI: 1.088–4.913, P=0.029), development of hypertension (OR=2.169, 95%CI: 1.180-3.984, P=0.013), and total gastrectomy (OR=2.444, 95%CI:1.214-4.013, P=0.012) were independent risk factors for postoperative sarcopenia in post-gastrectomy patients who had had gastric cancer ( P<0.05). Conclusion:Development of sarcopenia following radical gastrectomy demands attention. Older age, higher education, poor exercise habits, hypoproteinemia, hypertension, and total gastrectomy are risk factors for its development post-radical gastrectomy.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To investigate the impact of proximal versus total gastrectomy on survival outcomes in patients with advanced upper gastric cancer following neoadjuvant therapy, aiming to provide evidence-based guidance for optimal surgical approach selection.Methods:A retrospective cohort study was conducted to collect clinical data from 114 patients with upper gastric cancer who underwent surgical treatment after neoadjuvant therapy in the PLA General Hospital between November 2014 and November 2023, consisting of 96 males and 18 females, with an age range of 41 to 78 years and a median age of 64 years. According to the extent of surgical resection, 44 patients underwent proximal gastrectomy (PG), and 70 patients underwent total gastrectomy (TG). Propensity score matching was used to match patients with advanced upper gastric cancer who received proximal gastrectomy or total gastrectomy after neoadjuvant therapy based on factors such as gender, age, surgical approach, BMI, ypT stage, ypN stage, tumor size, R0 resection status, neoadjuvant therapy cycles, and neoadjuvant therapy regimen, with a 1∶1 matching ratio. In the end, 44 patients in the PG group and 44 patients in the TG group were successfully matched and analyzed. The primary outcomes were overall survival (OS) and disease-free survival (DFS), while secondary outcomes included operative duration, R0 resection rate, complication rate, total number of lymph nodes dissected, number of lymph nodes dissected in each group, and lymph node metastasis rate. Data analysis was performed using SPSS 25.0, and survival curves were generated using the Kaplan-Meier (K-M) method.Results:After propensity score matching, the operative time in the TG group was significantly longer than that in the PG group [(222.0±42.5) min vs (257.0±62.0) min, χ2=3.07, P=0.003], while the differences in other baseline characteristics between the two groups were not statistically significant ( P>0.05). In terms of postoperative complications, the incidence of Clavien-Dindo grade II or higher complications was 29.5% in the PG group and 34.1% in the TG group ( P=0.819), indicating no significant difference. The 5-year overall survival (OS) rates were 55.8% for the PG group and 49.5% for the TG group ( P=0.592), showing no statistically significant difference. Lymph node metastasis rates in the TG group were 5.71% (4/70) in group 4d, 4.29% (3/70) in group 5, 2.86% (2/70) in group 6, and 2.86% (2/70) in group 12a. Conclusions:For patients with advanced upper gastric cancer who undergo proximal gastrectomy or total gastrectomy following neoadjuvant therapy, there is no significant difference in perioperative complications and long-term survival rates. Therefore, proximal gastrectomy is a safe and reliable option for these patients, allowing partial preservation of gastric function and potentially improving quality of life.

Objective:To study the risk factors of complications after bowel resection for acute mesenteric ischemic disease.Methods:Retrospective case-control study was used to analyze the case data of 68 patients diagnosed with acute mesenteric ischemic disease (AMI) with bowel resection at the First Medical Center of the PLA General Hospital from January 2010 to January 2020, including 43 males and 25 females. The patients were divided into complication group ( n=21) and the non-complication group ( n=47) according to whether they had complications after surgery. The risk factors associated with the development of postoperative complications were analyzed by multivariate Logistic stepwise regression method to determine the risk factors with clinical significance. Measurement data with normal distribution were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups. Chi-square test was used for comparison between count data groups. Results:Univariate analysis showed that age >60 years, Marshall score≥2, type of resected bowel, pathology suggestive of irreversible transmural necrosis, length of ICU stay >6 d, length of mechanical ventilation >2 d, American Society of Anesthesiologists (ASA) classification, and preoperative procalcitonin≥2 ng/mL were the risk factors affecting the development of complications after bowel resection for acute mesenteric ischemic disease risk factors ( P<0.05). Multivariate Logistic regression analysis showed that age>60 years ( HR=12.364, 95% CI: 1.135-134.662, P=0.039) and preoperative procalcitonin ≥2 ng/mL ( HR=14.144, 95% CI: 1.280-156.303, P=0.031) were independent risk factors for the development of postoperative complications after AMI parallel bowel resection. Conclusion:The rate of complications after combined bowel resection for AMI is high. When patients are combined with age>60 years and preoperative procalcitonin≥2 ng/mL, preoperative prevention of postoperative complications should be emphasized to improve the prognosis of patients.

Objective:To investigate the risk factors for postoperative complications in emergency surgery for traumatic colon injury.Methods:In this study, a retrospective cohort study was used to collect the case data of 59 patients diagnosed with traumatic colon injury and emergency surgery in the PLA General Hospital from March 1, 2011 to March 31, 2023. According to whether complications occurred after emergency surgery, the patients were divided into the complication group( n=30)and the non-complication group( n=29). The main observation indexes were complication rate, Clavien-Dindo classification of complications, and risk factors related to complications. Normally distributed measurements were expressed as mean±standard deviation( ± s), and t-test was used for comparison between groups. Count data were compared between groups using the chi-square test. Clinically significant risk factors for predicting the occurrence of postoperative complications were determined by univariate and using multivariate logistic regression analysis. Results:A total of 56 occurrences of complications in 30 cases. 15 cases had multiple complications. Clavien-Dindo classification consisted of 23 cases of grade Ⅱ(41.1%), 1 cases of grade Ⅲa(1.8%), 6 cases of grade Ⅲb(10.7%), and 1 case of grade V(1.8%). The top three complication rates were 16 cases(28.6%) of pneumonia and(or) pleural effusion, 12 cases(21.4%) of incision infection, and 9 cases(16.1%) of postoperative bleeding. Univariate analysis showed that body mass index<24 kg/m 2, operation duration>235 min, intraoperative blood loss>100 mL, AAST-OIS grade≥4, preoperative serum albumin<35 g/L, preoperative white blood cell count>10×10 9/L, and preoperative procalcitonin≥2 ng/mL were risk factors for postoperative complications in traumatic colon injury underwent emergency surgery( P<0.05). Multivariate logistic regression analysis showed that body mass index<24 kg/m 2( OR=144.047, 95% CI: 3.695-5 614.986, P=0.008), preoperative serum albumin <35 g/L( OR=116.430, 95% CI: 3.582-3 784.038, P=0.007), preoperative procalcitonin≥2 ng/mL( OR=13.412, 95% CI: 1.030-174.662, P=0.047), and AAST-OIS grade≥4( OR=134.509, 95% CI: 3.934-4 599.473, P=0.007) were risk factors for postoperative complications in traumatic colon injury underwent emergency surgery. Conclusion:body mass index<24 kg/m 2, preoperative serum albumin<35 g/L, preoperative procalcitonin>2 ng/mL and AAST-OIS grade≥4 are risk factors for postoperative complications of traumatic colon injury. Early targeted treatment for patients with risk factors can help improve prognosis.

Objective:To investigate the risk factors of cervical lymph node metastasis (LNM) and survival analysis in patients with medullary thyroid carcinoma (MTC) .Methods:93 patients with MTC admitted to the Department of General Surgery and Department of Otorhinolaryngology, First Medical Center of PLA General Hospital from Sep. 2008 to Aug. 2020 were analyzed retrospectively, including 45 males and 48 females, with an average age of 47 years old. SPSS 26.0 statistical software was used for data processing of the initial surgical year and procedures, tumor pathological stages, preoperative calcitonin (Ctn) level, preoperative carcinoembryonic antigen (CEA) level, LNM status, recurrence free survival (RFS) , etc. The risk factors of LNM and prognosis of MTC patients were analyzed by COX univariate and multivariate regression. Kaplan Meier method was used to estimate the survival rates of independent risk factors affecting prognosis and draw their survival curves.Results:The median follow-up time of 93 patients was 53 months, ranging from 2 to 192 months. The 1-year, 3-year, 5-year and 10-year survival rates were 97.8%, 96.6%, 94.6% and 88.9% respectively. Multivariate COX regression analysis showed that Initial surgical procedures ( P=0.018) and preoperative Ctn level ( P=0.012) were independent risk factors of central cervical LNM. Preoperative Ctn level ( P=0.028) and Capsule invasion ( P=0.024) were the independent risk factors of lateral cervical LNM. Preoperative Ctn level≥180.30 pg/ml and ≥234.15pg/ml indicated central and lateral cervical LNM respectively (all P<0.001) . Distant metastasis was an independent risk factor of RFS ( P=0.037) of MTC. Conclusions:Standardized surgical procedures are recommended for initial treatment of MTC, which can reduce the possibility of residual occult metastasis and the risk of reoperation. Distant metastasis affects prognosis of MTC.

Objective:To analyze the effectiveness and safety of Morinidazole combined laparoscopic appendectomy for acute purulent appendicitis and acute gangrene appendicitis.Methods:We retrospectively retrieved 387 acute appendicitis patients who have received surgery or conservative treatment from Jan 2017 to Jun 2019. Firty four patients with Morinidazole + Etimicin bigeminy combined laparoscopic surgery were set to experimental group. The other 54 cases using ornidazole + levofloxacin bigeminy combined laparoscopic appendectomy were enrolled into control group after Propensity Score Matching.Results:After 1∶1 propensity score matching, there was no statistically significant difference between the two groups and control group in clinical features. The white blood cell count, C-reactive protein and calcitonin original inflammation index change were higher in experimental group than in the control group,both preoperatived and on post-op day1 and day 3 (all P<0.05). In the experimental group the length of hospital stay and analgesic drug usetime were shorter than in the control group (all P<0.05). Conclusion:Morinidazole combined laparoscopic appendectomy can effectively control the intra-abdominal infection caused by acute purulent appendicitis and acute gangrene appendicitis with less adverse reactions.