1.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
2.Study on the mechanism of Hongteng Decoction in inhibiting adenomyosis fibrosis from Hippo/YAP pathway
Weiwei ZENG ; Xinmin CHEN ; Lijuan LU ; Shenghui HUANG ; Yang CAO ; Tingting ZHANG
International Journal of Traditional Chinese Medicine 2024;46(7):867-873
Objective:To investigate the mechanism of Hongteng Decoction in inhibiting the adenomyosis (ADS) fibrosis by observing the effects on the key proteins of epithelial mesenchymal transformation (EMT), fibroblast-to-myofibroblast transformation (FMT) and Hippo pathway in uterine tissue of mice with ADS.Methods:ICR mice were divided into blank group, model group, Hongteng Decoction group, and verteporfin group according to random number table method, with 8 mice in each group. The day of birth of the mice was day 0, and from day 1, mice in model group, Hongteng Decoction group and verteporfin group were given 1 mg/kg tamoxifen solvent for gavage for 5 days. On the 42nd day after molding, HE staining verified that the molding was successful. Starting from the 43rd day, mice in the Hongteng Decoction group were given TCM solution of Hongteng Decoction 16.5 g/kg everyday, and intraperitoneally injected with 0.9%NaCl solution (100 μl/10 g) every 3 days. Mice in the verteporfin group were intraperitoneally injected with verteporfin solution of 100 mg/kg every 3 days, and intragastric with water of 100 μl/10 g everyday. Mice in blank group and model group were intragastric with constant volume of water daily and intraperitoneally injected with 0.9%NaCl solution every 3 days. The drugs were administered for 60 days. The fibrosis degree of mice in each group was evaluated by Masson staining. The expressions of E-cadherin, Vimentin, α-SMA, YAP and Snail in uterine tissue of mice in each group were detected by immunohistochemistry and Western blot.Results:Compared with the model group, the Masson staining expression in Hongteng Decoction group significantly decreased ( P<0.05). Immunohistochemical and Western blot analysis showed that the expression of E-cadherin in uterine tissue of mice in Hongteng Decoction group significantly increased ( P<0.05), while the expressions of Vimentin, α-SMA and YAP significantly decreased ( P<0.01, P<0.05) compared with the model group. Conclusion:Hongteng Decoction can inhibit the occurrence of EMT and FMT in ADS, thereby inhibiting fibrosis, and its mechanism is related to the regulation of Hipoo/YAP pathway.
3.Research progress on coloanal anastomosis techniques
Chinese Journal of Digestive Surgery 2024;23(6):782-788
Coloanal anastomosis is a surgical procedure in which the colon is connected to the anus after rectal resection, and it can be divided into one-stage immediate anastomosis and two-stage (delayed) coloanal anastomosis. Based on relevant literature and team practices, the authors explore the indications, technical essentials, complications, and functional aspects of both immediate and delayed coloanal anastomosis. When performing coloanal anastomosis, it should make rational choices based on the patient′s indications, condition, and actual technical situation of the surgeon. In sphincter-preserving surgery for low rectal cancer, the success of coloanal anastomosis depends on achieving effective reconstruction that ensures oncological safety, anatomical integrity, and func-tional recovery.
4.Morphology of the anterior mesorectum: a new predictor for local recurrence in patients with rectal cancer
Xiaojie WANG ; Zhifang ZHENG ; Min CHEN ; Jing LIN ; Xingrong LU ; Ying HUANG ; Shenghui HUANG ; Pan CHI
Chinese Medical Journal 2022;135(20):2453-2460
Background::Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer.Methods::A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology.Results::Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs. 16.3% [14/86], P = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014). Conclusions::The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.
5.Prognostic value of gastroepiploic lymph node metastasis in transverse colon cancer
Xiaojie WANG ; Shenghui HUANG ; Pan CHI ; Ying HUANG ; Daoxiong YE ; Yuxin XU
Chinese Journal of Digestive Surgery 2021;20(3):315-322
Objective:To investigate the prognostic value of gastroepiploic lymph node (GLN) metastasis in transverse colon cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 371 patients with transverse colon cancer who were admitted to Fujian Medical University Union Hospital from November 2010 to November 2017 were collected. There were 202 males and 169 females, aged from 21 to 92 years, with a median age of 58 years. Patients were performed complete mesocolic excision combined with GLN dissection by one group of surgeons. Of the 371 patients with transverse colon cancer, 15 cases had positive GLN metastasis (GLN+), and 356 cases had negative GLN metastasis (GLN-). Observation indicators: (1) the propensity score matching conditions and comparison of baseline data between GLN- patients and GLN+patients with transverse colon cancer after propensity score matching; (2) follow-up and survival of GLN- patients and GLN+patients with transverse colon cancer; (3) influencing factors for prognosis of patients with transverse colon cancer. Patients were followed up by outpatient examination or telephone interview to detect tumor metastasis and survival. Follow-up was conducted once every 3 months within postoperative 2 years, once every 6 months within postoperative 2-5 years and once a year thereafter up to January 2020. The propensity score matching was conducted by 1∶4 matching using the nearest neighbor method. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard regression model. The variables with P<0.10 in the univariate analysis were included for multivariate analysis. Results:(1) The propensity score matching conditions and comparison of baseline data between GLN- patients and GLN+ patients with transverse colon cancer after propensity score matching: 55 of 371 patients had successful matching, including 44 GLN- patients and 11 GLN+ patients. Before propensity score matching, the age, cases in stage 0 or stage 1 of M staging, preoperative carcinoembryonic antigen were 60 years(range, 24-92 years), 328, 22, 4.1 μg/L(range, 0.2-343.7 μg/L) for GLN- patients, respectively, versus 67 years(range, 21-79 years), 11, 4, 5.0 μg/L(range, 0.7-952.4 μg/L) for GLN+ patients, showing significant differences in the above indicators between the two groups ( Z=-1.440, χ2=9.031, Z=-2.086, P<0.05). After propensity score matching, the above indicators were 58 years(range, 45-67 years), 40, 4, 4.0 μg/L(range, 2.0-10.0 μg/L) for GLN- patients, respectively, versus 67 years(range, 59-71 years), 9, 2, 5.0 μg/L(range, 8.0-19.0 μg/L) for GLN+ patients, showing no significant difference between the two groups ( Z=-1.580, χ2=0.105, Z=-0.821, P>0.05). (2) Follow-up and survival of GLN- patients and GLN+ patients with transverse colon cancer: GLN- patients and GLN+ patients with transverse colon cancer were followed-up for 12-92 months and 1-70 months, with a median time of 53 months and 30 months respectively. Three cases of GLN- patients and 2 cases of GLN+patients had postoperative liver metastasis, respectively, showing no significant difference between the two groups ( χ2 =0.344, P>0.05). One case of GLN- patients and 3 cases of GLN+ patients had heterochronous lung metastasis, respectively, showing a significant difference between the two groups ( χ2 =4.870, P<0.05). The 5-year disease progression-free survival rates were 82.3% and 33.9% for GLN- patients and GLN+ patients, respectively, showing a significant difference between the two groups ( χ2 =13.366, P<0.05). (3) Influencing factors for prognosis of patients with transverse colon cancer: results of univariate analysis showed that pT staging, pN staging, M staging and GLN metastasis were related factors for prognosis of patients with transverse colon cancer ( hazard ratio=1.599, 5.107, 4.511, 6.273, 95% confidence interval as 0.467-5.471, 1.867-13.971, 1.385-14.694, 2.052-19.176, P<0.05). Results of multivariate analysis showed that pN staging, M staging and GLN metastasis were independent influencing factors for prognosis of patients with transverse colon cancer ( hazard ratio=6.399, 6.163, 4.024, 95% confidence interval as 2.028-20.189, 1.666-22.800, 1.177-13.752, P<0.05). Conclusion:For the patients with transverse colon cancer, GLN metastasis is associated with high postoperative heterochronous lung metastasis rate and poor prognosis. GLN metastasis is an independent prognostic factor for patients with transverse colon cancer.
6.Chylous ascites has a higher incidence after robotic surgery and is associated with poor recurrence-free survival after rectal cancer surgery.
Xiaojie WANG ; Zhifang ZHENG ; Min CHEN ; Shenghui HUANG ; Xingrong LU ; Ying HUANG ; Pan CHI
Chinese Medical Journal 2021;135(2):164-171
BACKGROUND:
Postoperative chylous ascites is an infrequent condition after colorectal surgery and is easily treatable. However, its effect on the long-term oncological prognosis is not well established. This study aimed to investigate the short-term and long-term impact of chylous ascites treated with neoadjuvant therapy followed by rectal cancer surgery and to evaluate the incidence of chylous ascites after different surgical approaches.
METHODS:
A total of 898 locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery between January 2010 and December 2018 were included. The clinicopathological data and outcomes of the patients with chylous ascites were compared with those of the patients without chylous ascites. The primary endpoint was recurrence-free survival (RFS). To balance baseline confounders between groups, propensity score matching (PSM) was performed for each patient with a logistic regression model.
RESULTS:
Chylous ascites was detected in 3.8% (34/898) of the patients. The incidence of chylous ascites was highest after robotic surgery (6.9%, 6/86), followed by laparoscopic surgery (4.2%, 26/618) and open surgery (1.0%, 2/192, P = 0.021). The patients with chylous ascites had a significantly higher number of lymph nodes harvested (15.6 vs. 12.8, P = 0.009) and a 3-day longer postoperative hospital stay (P = 0.017). The 5-year RFS rate was 64.5% in the chylous ascites group, which was significantly lower than the rate in the no chylous ascites group (79.9%; P = 0.007). The results remained unchanged after PSM was performed. The chylous ascites group showed a nonsignificant trend towards a higher peritoneal metastasis risk (5.9% vs. 1.6%, P = 0.120). Univariate analysis and multivariate analysis confirmed chylous ascites (hazard ratio= 3.038, P < 0.001) as an independent negative prognostic factor for RFS.
CONCLUSIONS
Considering the higher incidence of chylous ascites after laparoscopic and robotic surgery and its adverse prognosis, we recommend sufficient coagulation of the lymphatic tissue near the vessel origins, especially during minimally invasive surgery.
Chylous Ascites/etiology*
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Humans
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Incidence
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Laparoscopy
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Rectal Neoplasms/surgery*
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Retrospective Studies
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Risk Factors
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Robotic Surgical Procedures/adverse effects*
7.Research progress on sleep and allergic diseases in children and adolescents
LI Rong, HUANG Lili, WU Yani, LONG Siru, LI Shenghui
Chinese Journal of School Health 2021;42(6):939-943
Abstract
In recent years, the incidence of allergic diseases in children and adolescents has been on the rise globally, which has become an important public health problem. It is important to identify modifiable risk factors for allergic diseases in this group. In this paper, through research review on the association between sleep behavior and allergic diseases in children and adolescents, it is suggested that sleep deficiency, sleep disorder and sleep rhythm disturbance are closely related to children s allergic diseases, which provides a new concept for prevention of allergic diseases through sleep behavioral improvement.
8.Clinical efficacy of dual-kidney transplantation from infant donors to adult recipients
Mingchuan HUANG ; Chenglin WU ; Jun LI ; Xiaopeng YUAN ; Ronghai DENG ; Yitao ZHENG ; Longshan LIU ; Shenghui WU ; Xixi GAN ; Changxi WANG
Chinese Journal of Organ Transplantation 2021;42(1):8-13
Objective:To explore the clinical efficacy of dual-kidney transplantation from infant donors to adult recipients.Methods:From December 2012 to November 2020 in Organ Transplant Center First Affiliated Hospital Sun Yat-sen University, rertrospective reviews were conducted for clinical data of 25 pairs of infant donors and adult recipients. The survival rates were calculated for both recipients and transplanted kidneys at Year 1/3/5 post-transplantation. And the postoperative recovery status and the postoperative incidence of adverse events of recipients were observed.Results:The survival rates of recipients were all 95.8% at Year 1/3/5 and those of transplanted kidney and dealth-cancelling transplanted kidney all 87.2%. One case died due to acute inferior-wall cardiac infarction while three others lost renal functions for vascular thrombosis, ureteral stenosis and urinary fistula. Except for loss of renal function and death, the postoperative estimated golmerular fitration rate was (99.35±21.78), (103.11±29.20) and (114.99±28.55) ml/(min·1.73 m 2) at Year 1/2/3 respectively. Conclusions:Selecting proper recipients, standardizing donor acquisition and surgical procedures and strengthening perioperative managements may expand the donor pool. The overall outcomes are excellent for adult recipients with dual-kidney transplantation from donations after infants' death.
9.Prevalence of allergic diseases and associated factors among schoolaged children in Shanghai
Chinese Journal of School Health 2021;42(8):1251-1256
Objective:
To examine the prevalence of allergic diseases in schoolaged children from Shanghai and to explore related factors so as to produce epidemiological data regarding allergic diseases in children.
Methods:
Multistage cluster sampling was used to carry out the study in Shanghai from April to June 2019. A total of 10 686 children aged 7-12 years from 17 primary schools participated in the survey. The International Study of Asthma and Allergies in Childhood (ISAAC)Scale was used to evaluate allergic diseases. Multivariate Logistic regression analysis was performed to analyze the related factors.
Results:
The overall prevalence of allergic diseases among schoolaged children in Shanghai was 47.0%. A higher prevalence was observed among boys (50.4% vs 43.3% in girls, χ2=54.44, P<0.01). Common allergic diseases included asthma (13.9%), allergic rhinitis (18.2%), and atopic dermatitis (34.3%). The Logistic regression analysis showed that the common risk factors of asthma, allergic rhinitis and atopic dermatitis included the following:male gender (OR=1.52,1.44,1.22); mother has a bachelors degree or above (OR=1.26,1.77,1.84); family history of allergic diseases (OR=2.87,4.24,2.57); only child (OR=1.16,1.28,1.22); curtain cleaning frequency <1 time/month (OR=1.41,1.79,1.77); room not cleaned daily (OR=1.14,1.18,1.20); and dust exposure frequency ≥1 time/month (OR=1.45,1.56,1.42), all P<0.05. These three types of allergic diseases were also associated with unique risk factors that dependent on socialenvironmentalbehavioral factors.
Conclusion
Compared with previous data, the prevalence of allergic diseases among schoolaged children in Shanghai increased significantly in 2019. The related influencing factors involve multiple variables including demographics, environmental exposure and behavior, which warrant further exploration.
10.Construction of artificial neural network model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer
Shuangming LIN ; Xiaojie WANG ; Shenghui HUANG ; Zongbin XU ; Ying HUANG ; Xingrong LU ; Dongbo XU ; Pan CHI
Chinese Journal of Oncology 2021;43(2):202-206
Objective:To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer.Methods:A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log 2FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results:A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778.Conclusions:In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.


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