Retrospective multicenter nested case-control safety study of Ilaprazole sodium for injection / 中国药房

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

The significance of tumor deposits in prognosis and lymph node staging in gastric cancer patients / 中华普通外科杂志

Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.

10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation / 中国天然药物

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

The optimal means for measuring the abduction angle before Spica cast in developmental dysplasia of the hip / 中华骨科杂志

Objective:Comparison of four methods in intraoperative abduction angles (AA) measurements of human cast immobilization in developmental dysplasia of the hip (DDH) by visual inspection and electronic software according to different body surface markers.Methods:Data were retrospectively collected from January 2019 to November 2021 in a total of 27 patients (54 hips) who underwent closed or simple open reduction. There were 6 males and 21 females with an average age of 13.2 months. Five doctors used visual inspection and mobile phone software to measure the AA of the hip joint immediately during the operation, and compared with the postoperative MRI measurement results (AA-MRI). The four methods of intraoperative measurement were: Junior visualization (AA-JV), the intersection angle between the line connecting the center of the popliteal fossa and the contact center of the plaster frame and the line connecting the two ischial tuberosities; the same methods as method one by Senior visualization (AA-SV); the intersection angle between the line connecting the center of the popliteal fossa and the center of the anus and the line connecting the ischial tubercle (anus-popliteal, AA-AP); the intersection of the vertical line between the center of the popliteal fossa and the groin and the horizontal line of the center of the anus and the vertical line connecting the two ischial tuberosities intersect (anus-groin crease-popliteal, AA-AGCP). The t-test, correlation coefficient, linear regression and Bland-Altman test were used to evaluate the measurements. Results:Comparing the four intraoperative and postoperative AA-MRI measurement methods, AA-JV (42.69°±4.13°) < AA-SV (44.80°±4.08°) < AA-AGCP (46.25°±5.15°) < AA-MRI (47.68°±4.21°) < AA-AP (51.77°±5.30°), and the difference between AA-JV and AA-SV, AA-AP and AA-AGCP was statistically significant ( t=2.53, P=0.013; t=5.47, P=0.001), there was no significant difference between AA-AGCP and AA-MRI ( t=1.57, P=0.118). The inter-group agreement of the five methods ICC test ranged from 0.807 to 0.892, and the intra-group average agreement of AA-MRI was 0.948. All ICC results were greater than 0.75 with good agreement. Linear regression results showed that the four intraoperative measurement methods had a good or moderate linear relationship with AA-MRI, AA-AGCP ( R 2=0.499)>AA-AP ( R 2=0.318)>AA-SV ( R 2=0.253)>AA-JV ( R 2=0.217), AA-AGCP was the best measurement method. The results of Bland-Altman scatterplot of AA-AGCP and AA-MRI were in good agreement, the mean and standard deviation of bias were -0.796±3.247, and the limit of agreement was 95% LoA (-7.16, -5.57). Conclusion:The AA method of visualization before Spica casting was smaller than truth. The method AA-AGCP objectively by landmarks was the advocated means measuring abduction angle during operation with highly consistency, agreement and easily performed.

Progress of Lymphatic Navigation Technique in Minimally Invasive Surgery for Gastric Cancer / 肿瘤防治研究

The combination of standardized D2 lymph node dissection and lymph node sorting after surgery can improve the survival of patients with gastric cancer and increase the accuracy of staging. With the development of different lymphatic tracers, individualized lymphatic navigation has become a new technical breakthrough in minimally invasive surgery for gastric cancer. Lymph node tracing is an important method to improve the quality of intraoperative lymph node dissection and correct the postoperative pathological stage. This article reviews the application status and progress of lymphatic navigation technology.

Clinicopathological characteristics and lymph node metastasis in patients with early gastric cancer / 中华普通外科杂志

Objective:To explore the risk factors of lymph node metastasis (LNM) in early gastric cancer (ECG), and establish a risk-prediction model based on LNM.Method:Four hundred and twenty-seven EGC patients undergoing curative radical gastrectomy were enrolled in this study. The risk factors for LNM of ECG were analyzed with Logistic regression. LNM risk was stratified and risk-predicting model was established. The risk-predicting model was measured by area under ROC curve. According to the same standard, clinical data of 133 patients with EGC who underwent radical surgery were selected for external verification of the model.Results:The frequency of LNM was 13.3% (32/427) in EGC patients. The LNM ratio of intramucosal carcinoma and submucosal carcinoma was 1.3% (3/237), 15.3% (29/190) respectively. Ulcer presence, tumor size >2 cm, undifferentiated tumor, submucosal invasion, neural invasion, and vascular tumor thrombus were significantly associated with LNM in EGC patients ( χ2=3.408, 16.379, 4.808, 29.804, 25.305, 47.120, respectively P<0.05). Multivariate analysis suggested that ulcer presence, tumor size >2 cm, depth of invasion, neural invasion, and vascular tumor thrombus were independent predictors of LNM in EGC patients, ( OR=0.326, 2.924, 11.824, 13.047, 7.756, respectively P<0.05). LNM predicting model is established, P=e

Influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junction treated by neoadjuvant chemoradio-therapy combined with surgical resection: a prospective study / 中华消化外科杂志

Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date 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 analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.

Laparoscopic or robotic serosa muscular layer circumferential incision combined with mucosal layer cutting and closure for gastrointestinal mesenchymal tumors at difficult sites of the stomach / 中华普通外科杂志

Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.

Construction and analysis of the structural equation model for the influencing factors of endothelial function of the brachial artery / 中华健康管理学杂志

Objective:To examine the influencing factors of endothelial injury using the structural equation model (SEM).Methods:A total of 6 861 asymptomatic individuals free of cardiovascular disease underwent health examinations at the health management center of the third Xiangya hospital, Central South University from May 2015 to August 2020. And collected their questionnaire and checkup data. Spearman′s rank correlation coefficient was used to analyze metabolic factors and brachial artery flow-mediated dilatation (FMD). Exploratory factor analysis (3 430/6 861) and confirmatory factor analysis (3 431/6 861) were conducted on the diet items. An SEM was constructed using the diet pattern data, cardiovascular risk factors and FMD, and using multi-path regression analysis to determine the correlation between the indicators.Results:Based on the factor analysis, diet items were divided into three patterns: healthy food, meat, and supplementary food. The SEM indicated that age ( β=0.27) and blood pressure ( β=0.12) had obvious effects on low FMD. Triglyceride ( β=0.03), fasting blood glucose ( β=0.04), and body mass index ( β=0.08) were positively correlated with low FMD. On the upstream, healthy food was negatively correlated with blood pressure ( β=-0.04) and body mass index ( β=-0.04), meat was positively correlated with triglyceride ( β=0.33), blood pressure ( β=0.06), fasting blood glucose ( β=0.20), and body mass index ( β=0.16), and supplementary food was negatively correlated with fasting blood glucose ( β=-0.30). This was the only pattern that was directly correlated with FMD ( β=0.05). Conclusions:SEM is an effective method to analyze the influence of various risk factors on the population and the relationship between individual indicators. This study revealed direct and indirect correlations between age, diet pattern, cardiovascular-metabolic risk, and FMD impairment. Comprehensive control of dietary patterns and metabolic indicators could prevent and improve early cardiovascular injury.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial / 中华胃肠外科杂志

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

Clinicopathological Characteristics and Prognosis of Borrmann Type Ⅳ Gastric Cancer / 肿瘤防治研究

Objective To investigate the clinicopathological characteristics and prognosis of patients with Borrmann type Ⅳ gastric cancer. Methods A cohort retrospective analysis of 2386 patients with gastric cancer who underwent radical surgery was used to screen out Borrmann type Ⅳ patients, and analyze their clinical features and prognostic factors. Results Among 2386 patients with gastric cancer, 363 cases (15.21%) were Borrmann type Ⅳ. Compared with non-Borrmann type Ⅳ gastric cancer patients, Borrmann type Ⅳ patients had higher rates of simultaneous liver metastasis, metachronous liver metastasis, lymph node metastasis and vascular infiltration. Moreover, the age of onset tended to be younger and the pathological type tended to be poorly differentiated-undifferentiated (all P < 0.05). The 5-year OS of the entire group was 49.32% and the 5-year DFS was 44.61%. There were significant differences in 5-year OS and DFS between Borrmann type Ⅳ and non-Borrmann type Ⅳpatients (all P < 0.001). The subgroup analyses showed that there were statistically significant differences in 5-year OS and DFS of gastric cancer patients between Borrmann type Ⅳ and non-Borrmann type Ⅳ in pT2-pT4a and pN0-pN3a stages (all P < 0.005). Multivariate analysis showed that the poorly differentiated-undifferentiated tumor, the T4a-pT4b stage of tumor invasion depth, lymph node metastasis, the ⅢA-ⅢC pTNM stage of the tumor, postoperative liver metastasis and peritoneal metastasis were independent risk factors affecting the prognosis of Borrmann type Ⅳ gastric cancer patients (all P < 0.05). Conclusion Borrmann type Ⅳ gastric cancer is prone to liver metastasis, lymph node metastasis, peritoneal metastasis and poor prognosis, and it's prognosis is affected by a variety of independent risk factors.

Correlation between systemic immune-inflammation index and prognosis of patients with gastric cancer after radical resection / 中华消化杂志

Objective:To investigate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophils, lymphocytes and platelets counts in predicting the prognosis of patients with gastric cancer after radical resection.Methods:From January 1, 2012 to January 1, 2015, the data of 2 273 patients with gastric cancer who underwent radical surgery at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. SII value was calculated according to the formula (SII=neutrophil cell count (×10 9/L)×platelet cell count (×10 9/L)/lymphocyte count (×10 9/L)). According to receiver operating characteristic curve (ROC), the optimal cut-off value of SII was determined and the patients were divided into high SII group and low SII group. Chi-square test was used to compare the clinicopathological characteristics and prognosis of the two groups. Kaplan-Meier method was applied to draw survival curve, log-rank test was used for univariate survival analysis, and Cox regression model was used for multivariate survival analysis. The ROC of preoperative SII, pathological TNM stage and their combination for predicting prognosis and recurrence were drawn, and the area under the curve (AUC) values were calculated to compare the predictive power of the three. Results:According to the ROC, the optimal cut-off value of SII was 589.5, and there were 1 180 cases (51.91%) in the high SII (SII≥589.5) group and 1 093 cases (48.09%) in the low SII (SII<589.5) group. Compared with those of the low SII group, the maximum diameter of gastric cancer in the high SII group was mostly ≥5 cm (49.04%, 536/1 093 vs. 56.27%, 664/1 180), the histological types were mostly poorly differentiated to undifferentiated (55.63%, 608/1 093 vs. 61.19%, 722/1 180), the depth of tumor invasion was mainly from T4a to T4b (45.11%, 493/1 093 vs. 54.837%, 647/1 180), and the rate of lymph node metastasis, pathological TNM stage, rate of vascular infiltration, incidence of nerve invasion, Ki-67 expression level, serum carcinoembryonic antigen level and carbohydrate antigen 19-9 level in the high SII group were all higher than those in the low SII group (67.70%, 740/1 093 vs. 80.68%, 952/1 180; 57.64%, 630/1 093 vs. 71.10%, 839/1 180; 55.54%, 607/1 093 vs. 67.03%, 791/1 180; 53.89%, 589/1 093 vs. 64.32%, 759/1 180; 45.29%, 495/1 093 vs. 56.69%, 669/1 180; 56.91%, 622/1 093 vs. 63.20%, 734/1 180; 53.25%, 582/1 093 vs. 57.97%, 684/1 180), and the differences were statistically significant ( χ2=8.842, 11.097, 7.225, 21.467, 50.200, 44.984, 31.687, 25.594, 29.549, 6.612 and 5.119, all P<0.05). The 5-year overall survival rate and disease-free survival rate of the low SII group were 75.66% and 67.61%, respectively, which were both higher than those of the high SII group, (24.92% and 23.31%, respectivily), the differences were statistically significant ( χ2=620.700 and 413.00, both P<0.01). The results of multivariate Cox regression analysis showed that tumor histological type, depth of invasion, pathological TNM stage, vascular invasion and preoperative SII were independent risk factors for postoperative prognosis and recurrence of patients with gastric cancer (odds ratios were 4.126, 2.255, 5.123, 3.826, 6.126, 4.683, 2.472, 5.224, 4.416, 6.212, respectively; 95% confidence interval 2.123 to 9.721, 1.632 to 7.427, 3.325 to 10.211, 2.321 to 9.322, 4.127 to 13.782, 2.561 to 9.418, 1.322 to 6.289, 3.315 to 11.526, 2.213 to 9.382, 4.474 to 13.541; all P<0.05). The predictive power of preoperative SII (AUC=0.842, 0.815) and pathological TNM stage (AUC=0.881, 0.827) for the 5-year overall survival and disease-free survival of patients with gastric cancer after radical resection was similar, however the predictive power of combination of the two (AUC=0.943, 0.895) was higher than that of preoperative SII and pathological TNM stage alone. Conclusions:Preoperative SII is an independent risk factor for the prognosis of patients with gastric cancer after radical resection, combined with parthological TNM stage can be used as an indicator to predict the prognosis and recurrence of patients.

Effect of specific small interfering RNA against KLF11 expression on proliferation and apoptosis of human gastric cancer cell line BGC823 via Wnt/β-catenin signaling pathway / 中华普通外科杂志

Objective:To investigate the expression of KLF11 in gastric cancer tissues and cell lines as well as its effect on proliferation and apoptosis of human gastric cancer cells BGC823.Methods:Sixty pairs gastric cancer tissues and corresponding adjacent tissues were collected. The expression of KLF11 mRNA in gastric cancer tissues and their adjacent tissues was detected by RT-PCR. The expression of KLF11 was detected in gastric cancer cells. KLF11 expression was silenced. The proliferation of cells were detected by using MTT assay. Flow cytometry was used to detect the cell cycle and cell apoptosis rate. Western bloting was used to examine the changes of concentration of proteins associated with cell cycle,cell apoptosis and Wnt/β-catenin signaling pathway related proteins. The activity of Caspase3 enzyme was detected by spectrophotometry.Results:The relative expression of KLF11 mRNA in gastric carcinoma tissues was significantly higher than that of the adjacent tissues ( t=11.38, P<0.05). Its expression was related to tumor size, depth of invasion, lymph node metastasis and TNM clinical stage (all P<0.05). The proliferation of BGC823 cells was significantly suppressed after KLF11 silencing ( F=19.56, P<0.05), and the cell cycle was arrested in G 0/G 1 phase [(41.40%±0.98%) vs. (66.53%±1.01%), F=32.69, P<0.05]. Meanwhile, the apoptosis rate was significantly increased by KFL11 silencing [(41.44%±1.59%) vs. (15.42%±0.86%), F=35.35, P<0.05]. The results of Western blotting revealed that the expression of Bax and Cleaved Caspase3 was significantly increased ( F=23.33, 33.63; both P<0.05), wheras that of β-catenin, Bcl-2, CyclinD1and CyclinE was significantly reduced ( F=22.21, 16.24, 26.75, 33.42; all P<0.05). The activity of Caspase3 enzyme was enhanced ( F=16.56, P<0.05). Conclusion:KLF11 was highly-expressed in gastric cancer tissues and cells, KFL11 silencing could inhibit gastric cancer cells proliferation and induce cell apoptosis via Wnt/β-catenin signaling pathway.

Risk factors relating to lymphatic leakage and prediction scoring model after radical gastrectomy for gastric carcinoma / 中华普通外科杂志

Objective:To explore the risk factors of lymphatic fistula after radical gastric cancer operation.Methods:We retrospectively analyze the clinicopathological data of gastric cancer patients who underwent radical surgery from May, 2019 to May, 2020 at the Third Department of Surgery, Fourth Hospital of Hebei Medical University, and analyze the risk factors impacting postoperative lymphatic leakage,for the establishment of the risk prediction scoring model.Results:A total of 487 patients with gastric cancer underwent radical gastrectomy, of which 32 patients (6.6%) had lymphatic leakage . Multivariate logistic regression analysis showed that hypoproteinemia before surgery (95% CI: 1.222-7.357, P=0.016), the lesion is located in the cardia-fundus of the stomach (95% CI: 1.117-6.788, P=0.028),stage T3-T4 (95% CI: 1.149-25.676, P=0.033), operation time ≥4 h (95% CI: 1.469-11.480, P=0.007), combined organ resection (95% CI: 1.106-12.886, P=0.034), D2+ lymph node dissection (95% CI: 1.969-11.510, P=0.001), anemia (95% CI: 1.271-9.392, P=0.015) were an independent risk factors. Equation based on multi-factor Logistic regression: logit( P)=-9.624+1.098×X 1+1.013×X 2+1.692×X 3+1.413×X 4+1.328×X 5+1.560×X 6+1.240×X 7 was estaslished, using Hosmer. Lemeshow test detects the goodness of fit of the regression equation ( P=0.348). The area under the ROC curve was 0.856 (95% CI: 0.787-0.926, P<0.001); the probability of lymphatic leakage when scores ≥4 points was 14.1%, when scores <4 points ,the probability of leakage was 2.5%. Conclusion:A risk prediction scoring model for lymphatic leakage after radical gastrectomy, can identify patients with high risk after surgery

Application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.

Related risk factors analysis of pancreatic fistula after radical resection of gastric cancer and establishment of risk prediction scoring model / 肿瘤研究与临床

Objective:To investigate the risk factors of pancreatic fistula after radical resection of gastric cancer, and to establish a risk prediction scoring model for pancreatic fistula.Methods:The clinico-pathological data of 312 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from January 2019 to January 2020 were retrospectively analyzed. Multiple factor logistic regression model was used to analyze the risk factors of pancreatic fistula after radical resection of gastric cancer, and a risk prediction scoring model based on the risk factors was established. Hosmer-Lemeshow test was used to detect the goodness of fit of regression equation, and receiver operating characteristics (ROC) curve was used to evaluate the distinction degree of regression equation.Results:Among 312 patients with gastric cancer, 27 cases (8.65%) had pancreatic fistula after radical resection of gastric cancer. Multiple factor logistic regression analysis showed that male patients ( OR = 5.312, 95% CI 1.532-18.420, P = 0.008), age ≥ 60 years old ( OR = 4.928, 95% CI 1.493-16.250, P = 0.009), preoperative diabetes mellitus ( OR = 3.062, 95% CI 1.091-8.589, P = 0.034), lesion location in the gastric body-gastric antrum ( OR = 3.121, 95% CI 1.052-9.251, P = 0.040), intraoperative omental bursa resection ( OR = 6.209, 95% CI 2.084-18.478, P = 0.001), intraoperative lymph node dissection at D2+ station ( OR = 3.114, 95% CI 1.044-9.281, P = 0.042), intraoperative combined organ resection ( OR = 5.063, 95% CI 1.473-17.400, P = 0.010), preoperative TNM stage Ⅲ ( OR = 4.973, 95% CI 1.189-20.792, P = 0.028) were independent risk factors for pancreatic fistula after radical resection of gastric cancer. A risk prediction equation of pancreatic fistula after radical resection of patients with gastric cancer was established: P = -8.619+1.670X 1+1.595X 2+1.119X 3+1.138X 4+1.826X 5+1.136X 6+1.622X 7+1.604X 8; factor X was set as a binomial assignment (0 or 1); X1-X8 were listed as follows respectively: gender (the male was 1), age (≥60 years old was 1), preoperative diabetes history (yes was 1), lesion location (gastric body-gastric antrum was 1), intraoperative resection of omental bursa or not (yes was 1), intraoperative lymph node dissection at D2+ station or not (yes was 1), intraoperative combined organ resection or not (yes was 1), preoperative TNM stage (stage Ⅲ was 1). The goodness of fit of regression equation was high ( P = 0.395). The area under the curve of ROC by using risk prediction scoring model to judge pancreatic fistula was 0.916 (95% CI 0.872-0.960, P<0.01). The probability of pancreatic fistula in patients with score ≥ 5 was 40.90%, and the probability of pancreatic fistula in patients with score < 5 was 3.35%. Conclusions:The occurrence of pancreatic fistula after radical resection of gastric cancer is closely related to a variety of risk factors. By establishing a risk prediction scoring model for pancreatic fistula after radical resection of gastric cancer, it is helpful to effectively identify patients with high risk of pancreatic fistula after radical surgery during the perioperative period.

Clinicopathologic parameters and prognostic analysis of progressive disease after neoadjuvant therapy for locally advanced gastric cancer / 中华普通外科杂志

Objective:To investigate the clinically relevant factors of progressive disease (PD) after neoadjuvant therapy for locally advanced gastric cancer.Methods:From Jun 2011 to Mar 2016, 569 patients with locally advanced gastric cancer(cT3/4N0/+ M0) admitted to the Fourth Hospital of Hebei Medical University were retrospectively analyzed .Results:All 569 patients completed neoadjuvant therapy, 59 patients (10.4%) had PD. Univariate analysis showed that tumor size (χ 2=10.091, P=0.001), pathological type (χ 2=4.110, P=0.043), Borrmann type (χ 2=91.941, P=0.001), pre-treatment cT stage (χ 2=7.980, P=0.005) were associated with PD after neoadjuvant therapy for gastric cancer. The results of multi-factor regression analysis showed that pathological type, Borrmann type, pre-treatment cT stage were independent factors influencing the occurrence of PD after neoadjuvant therapy for advanced gastric cancer. The overall survival and progression-free suruival time of patients with PD is significantly shorter than that of patients without PD . Conclusion:The pathological type, Borrmann typing and pre-treatment cT stage are the influencing factors for the occurrence of PD after neoadjuvant treatment in advanced gastric cancer, and the prognosis of PD patients is poor.

Analysis of clinico-pathological features and risk factors affecting prognosis in elderly patients with gastric cancer / 中华老年医学杂志

Objective:To explore the clinico-pathological characteristics and risk factors affecting prognosis in elderly patients with gastric cancer.Methods:A retrospective study was used to retrospectively analyze 2386 patients with gastric cancer undergoing radical surgery in Surgery Department of the Fourth Hospital of Hebei Medical University from 1 January 2012 to 1 January 2015.Patients aged 70 years and older were screened so as to analyze clinical characteristics and influencing factors for the prognosis.Results:A total of 2386 patients with gastric cancer were divided into the elderly group aged 70 years and older(342 of 2386 cases, 14.3%). There were statistically significant differences between the two groups in gender, number of concomitant diseases, NRS2002 score, PG-SGA score, tumor location, tumor diameter, histological type, Borrmann classification, tumor invasion depth staging(pT), lymph node metastasis staging(pN), the anatomic extent of tumor staging(TNM, pTNM), and Lauren classifications( P<0.05). The 981 of 2386 cases(41.4%)had postoperative complications, accompanied by 413 cases(17.3%)of surgery-related complications and 568 cases(24.0%)of non-surgery-related complications.A multivariate logistic analysis showed that the number of preoperative co-existing diseases ≥ 2 was an independent influencing factor for postoperative complications in elderly gastric cancer patients( HR=4.478, 95% CI: 1.121-7.918, P=0.006). The 5-year OS and DSS was 21.10% and 62.73% in the ≥70 years gastric cancer group, and was 54.1% and 70.0% in the <70 years gastric cancer group, respectively.The difference in the 5-year OS between the two groups was statistically significant( P<0.05), while the difference in the 5-year DSS between the two groups was not statistically significant( P>0.05). Multivariate analysis by the Cox proportional hazard model showed that the independent risk factors for the prognosis of elderly patients with gastric cancer included the low-undifferentiated histological type of the tumor( P=0.004), the depth of tumor invasion pT stage of pT4a-pT4b( P=0.007), lymph node metastasis( P=0.034), tumor pTNM stage ⅢA-ⅢC( P=0.002)and vascular tumor thrombus( P=0.034). Conclusions:Elderly patients with gastric cancer have many preoperative co-existing diseases, which increases the risk of postoperative non-surgical complications.Therefore, we should focus on the peri-operative management of their comorbid diseases so as to improve the safety and efficacy of surgery.The advanced age is not the independent risk factors for the prognosis.

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells / 医学前沿

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.