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In 2022, the European Association for the Study of the Liver issued Clinical practice guidelines on sclerosing cholangitis. With reference to the 2017 edition of Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline (2017) and in comparison to the corresponding contents in Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) issued by Chinese Society of Hepatology, Chinese Medical Association, in 2021, this article summarizes the updates in diagnosis, treatment, monitoring, and management of special populations and analyzes the basis for updated recommendations and their guiding significance in optimizing the clinical management of primary sclerosing cholangitis (PSC). The comparative analysis shows that the new version of the guidelines is similar to the Chinese guidelines in terms of diagnosis, treatment, and follow-up, and it is worth learning from the technical details such as the recommended dose of ursodeoxycholic acid and long-term follow-up plan. Since PSC is a chronic refractory disease, the drugs recommended by current guidelines cannot delay or reverse disease progression, and there is still a lack of consensus statements on immunotherapy and screening protocols for end-stage complications, which might be the directions for further research.
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Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.
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Animals , Bees/genetics , Larva/metabolism , RNA, Circular/genetics , RNA, Small Interfering/genetics , MicroRNAs/geneticsABSTRACT
Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.
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Objective:To analyze the radiological protection situation in the workplace of medical X-ray diagnostic equipment in primary medical institutions in south Xinjiang Uygur Autonomous Region, and then put forward necessary measures and suggestions.Methods:In accordance with the national medical radiation protection monitoring program and the requirements of relevant standards for radiological health, medical X-ray diagnostic equipment in radialogical diagnosis and treatment institutions was tested selectively for workplace radiological protection, with the result statistically analyzed.Results:From 2018 to 2021, radiological protection test was conducted for 84 workplaces in 15 radiological diagnosis and treatment institutions in 4 districts of south Xinjiang, with a pass rate of 98.8%, which was consistent with the mainland including the eastern and central regions in the country.Conclusions:Based on the current situation in radiological diagnosis and treatment institutions on medical radiation protection in south Xinjiang, it is recommended to strengthen the supervision and management of radiological diagnosis and treatment equipment, improve the testing and technical capabilities of the local medical radiation monitoring technical teams and raise the level of radiological health work in the south Xinjiang.
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Exosomes (EXOs) are formed by intracellular multivesicular bodies and carry a variety of biomacromolecules such as lipids, proteins, encoding and non-coding RNAs, and mitochondrial DNA. EXOs can be released in vivo by different cell types, including hepatocytes, hepatic stellate cells, and immune cells and play the role of intercellular communication. More and more studies have shown that EXOs are involved in the development, progression, and prognosis of chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection and are expected to become potential biomarkers for the early diagnosis and prognostic evaluation of HBV-related HCC. This article reviews the role of EXOs in the host infection process of HBV and the importance of EXOs in the development, progression, and prognosis of CHB and HCC, in order to provide new ideas for the basic and clinical research in this field.
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Objective To establish a new N-stage system combining the number of metastatic lymph nodes and the ratio of metastatic lymph nodes for postoperative M0 stage inflammatory breast cancer patients. Methods Based on the data of inflammatory breast cancer patients in the SEER database, the number of metastatic lymph nodes and the ratio of metastatic lymph nodes were calculated.A new N-staging system was established and compared with the 8th edition of AJCC TNM staging system of breast cancer.The nomograph prognostic model was constructed and validated. Results The prediction performance of the new N-staging system for postoperative survival of M0 inflammatory breast cancer patients was better than the traditional N-staging system.The nomograph prognostic model showed an excellent clinical efficacy with a consistency index of 0.711. Conclusion The new N-staging system has good predictive performance for postoperative survival of M0 inflammatory breast cancer patients and can accurately reflect the prognosis.
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To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%), P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.
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Intestinal flora is closely associated with chronic hepatitis B (CHB). Recent studies have shown that the imbalance of intestinal flora is associated with the development, progression, and prognosis of CHB, and the environment of intestinal flora may also change with disease progression, suggesting that intestinal flora and CHB interact with each other. This article reviews the influence of intestinal flora on the progression of CHB and related liver diseases and the role of intestinal flora regulation in the diagnosis and treatment of CHB and related liver diseases, in order to provide new ideas for the clinical treatment of CHB.
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BACKGROUND@#Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).@*METHODS@#A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.@*RESULTS@#In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).@*CONCLUSION@#This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
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Humans , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Network Meta-Analysis , Pharmaceutical Preparations , Randomized Controlled Trials as Topic , Tuberculosis/drug therapyABSTRACT
CCL20 and CCR6 are chemokines produced by a variety of cells. CCL20 and CCR6 combine to stimulate a series of downstream pathways, participate in the occurrence and development of various malignant tumors, and also play an important role in the invasion and metastasis of breast cancer and the process of chemotherapy resistance. Epithelial-mesenchymal transformation (EMT) is a key step in the process of tumor cell metastasis, which is characterized by loss of cell adhesion, down-regulation of E-cherherin expression, up-regulation of mesenchymal markers and fibrinectin expression, and enhancement of cell motor ability and invasion ability. This article reviews the research of CCL20-CCR6 biological axis and EMT on invasion and metastasis of breast cancer cells.
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The axillary lymph node status is the most important prognostic index of breast cancer, so the accurate assessment of axillary lymph node metastasis has always been a hot topic in breast cancer research. Today, sentinel lymph node biopsy (SLNB) has become the preferred surgical procedure for axillary lymph node negative early breast cancer. The selection of tracers is also a key link in the study of SLNB and lymphatic drainage area of breast cancer. Traditional tracers (blue dye, nuclide and fluorescent tracers, etc.) have many problems, such as allergy, poor localization specificity and radioactivity to human body, which limit their promotion and application in clinic. However, superparamagnetic iron oxide nanoparticle (SPION) can effectively improve these shortcomings and has the advantages that other tracers cannot replace. It can be an ideal tracer for SLNB of breast cancer and has a good application prospect. This article mainly describes the current application of SPION in SLNB of breast cancer, and outlines the advantages and disadvantages of this tracer.
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Herein, we report a novel sensor to detect trypsin using a purpose-designed fluorescein-labelled peptide with negatively charged carbon nanoparticles (CNPs) modified by acid oxidation. The fluorescence of the fluorescein-labelled peptide was quenched by CNPs. The sensor reacted with trypsin to cleave the peptide, resulting in the release of the dye moiety and a substantial increase in fluorescence intensity, which was dose-and time-dependent, and trypsin could be quantified accordingly. Correspondingly, the biosensor has led to the development of a convenient and efficient fluorescent method to measure trypsin activity, with a detection limit of 0.7μg/mL. The method allows rapid determination of trypsin activity in the normal and acute pancreatitis range, suitable for point-of-care testing. Furthermore, the applicability of the method has been demonstrated by detecting trypsin in spiked urine samples.
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Autologous fat grafting (AFG) is a new postoperative plastic technique for breast cancer. The safety of this technique in oncology is a controversial issue in academic circles. In some basic experiments, it was found that adipocytes could promote the proliferation of surrounding cancer cells through autocrine and paracrine. However, clinical trial data show that this procedure does not increase the risk of postoperative recurrence or metastasis of breast cancer. Nowadays, there are variety of researches on the safety of this technique, but many limitations are found in these trials. Therefore, to accurately assess the relevance of these studies to any realistic clinical risk, it is necessary to include large sample of clinical studies. In this paper, the data of basic experiments and clinical trials in recent ten years were collected, and the safety of oncology was further analyzed and discussed, which will provide reference for clinical decision-making of postoperative breast reconstruction.
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Exosomes play an important role in the early diagnosis of various diseases, and it is a research hotspot in recent years. Exosomes are vesicles with a diameter of 30 to 100 nm secreted by cells, which widely exist and distribute in various body fluids. They carry a large number of specific proteins and functional substances, and participate in the transmission of intercellular substances and information, including tumor metastasis, immunity, cardio cerebral vascular, stem cell therapy, as well as immune regulation, targeted drug delivery, tissue damage repair, etc., forming It is an ideal biomarker. In this paper, the latest research progress of the main components of exosomes (miRNA, protein, mRNA, lncRNA, piRNA, circRNA, DNA and so on) in breast cancer in recent years is reviewed.
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As one of the most common malignant tumors in women,breast cancer has the characteristics of high inc idence,strong invasion,easy recurrence and metastasis.Although the mortality of breast cancer has decreased in recent years,its incidence has not been effectively controlled.Chemoprevention is a kind of preventive measure to reduce the incidence of disease by using natural or synthetic chemical drugs to prevent the asymptomatic high-risk population.At present,only estrogen receptor modulators and aromatase inhibitors are allowed to be used in clinical chemoprevention of breast cancer.Therefore,researcher should actively take measures to find new highefficient,low-toxic chemoprevention agents that take into account the majority of the population.The main purpose of this review is to summarize the mechanisms and related experimental studies of six chemoprevention agents for breast cancer including estrogen receptor modulators,include aromatase inhibitors,aspirin,metformin,flavones and poly(ADP-ribose) polymerases inhibitors.
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As one of the most common malignant tumors in women, breast cancer has the characteristics of high incidence, strong invasion, easy recurrence and metastasis. Although the mortality of breast cancer has decreased in recent years, its incidence has not been effectively controlled. Chemoprevention is a kind of preventive measure to reduce the incidence of disease by using natural or synthetic chemical drugs to prevent the asymptomatic high-risk population. At present, only estrogen receptor modulators and aromatase inhibitors are allowed to be used in clinical chemoprevention of breast cancer. Therefore, researcher should actively take measures to find new high-efficient, low-toxic chemoprevention agents that take into account the majority of the population. The main purpose of this review is to summarize the mechanisms and related experimental studies of six chemoprevention agents for breast cancer including estrogen receptor modulators, include aromatase inhibitors, aspirin, metformin, flavones and poly(ADP-ribose) polymerases inhibitors.
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Objective:To evaluate the association of maternal nutrition status in the first trimester with gestational diabetes mellitus (GDM) and macrosomia.Methods:378 pregnant women who took prenatal care in Shunyi Women′s and Children′s Hospital of Beijing Children′s Hospital were enrolled in the study. Blood samples were collected at first prenatal visit (<12 gestation weeks) to measure the level of hemoglobin and iron status indexes including serum iron, ferritin, transferrin, total iron binding capacity, iron saturation, transferrin saturation. The incidence of GDM and macrosomia were collected and Logistic regression was used to evaluate the associations of maternal nutrients status in the first trimester with GDM and macrosomia.Results:The incidence rate of GDM was16.9%,the incidence of anemia and iron deficiency in the first trimester were2.4% and 2.5%, respectively. After adjustment for variables such as maternal age, pre-pregnancy BMI, family history of diabetes, and parity, Logistic regression showed that in the first trimester, iron saturation>50% ( OR=0.238, 95% CI 0.068-0.831), transferrin saturation>50% ( OR=0.08, 95% CI 0.010-0.677) were protective factors of GDM; iron saturation 25%-50% ( OR=0.361, 95% CI 0.143-0.908); transferrin saturation 25%-50% ( OR=0.383, 95% CI 0.165-0.891); ferritin>30 ng/ml ( OR=0.418, 95% CI0.186-0.939) were protective factors of macrosomia. Conclusion:Maternal iron status in the first trimester might be associated with GDM and macrosomia. Thus, maternal iron status assessment in the first trimester is necessary.
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Objective To investigate the effects of vitamin D3 supplementation combined with standard-ized hypoglycemic regimen on islet β cell function and macroangiopathy of T2DM patients. Methods A total of 192 patients with type 2 diabetes mellitus were selected and randomly divided into control group and observation group with 96 patients in each group. Patients in two groups were given standardized hypoglycemic regimen, and the observation group was treated with vitamin D3 supplementation in addition. The changes of the indexes of body examination, glycolipid metabolism, islet β cell function and macrovascular complications before and 6 months after treatment were compared between the two groups. Results After 6 months of treatment, BMI, SBP, TG, FBG, FINS, HbA1c and HOMA-IR decreased, while HOMA-β increased in both groups ( P<0. 05) . Compared with the control group, the serum levels of 25 ( OH) D increased, and vaspin and CRP de-creased significantly after 6 months of treatment in the observation group ( P<0. 05) . CIMT and other indicators showed no significant difference. 25 (OH) D was negatively correlated with FBG, FINS, vaspin and CRP, and positively correlated with 1PH and ISI (P<0.05). Conclusion Vitamin D3 is closely related to T2DM and its macrovascular complications, but it has not been found that vitamin D3 supplementation can further improve islet β cell function and macrovascular complications in patients with T2DM.
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Objective@#To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test.@*Methods@#One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing.@*Results@#The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients.@*Conclusions@#The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.
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Objective To evaluate the defecation function of patients with low rectal cancer after laparoscopic-assisted transanal total mesorectal excision (TaTME),and analyze the influencing factors.Methods The retrospective case-control study was conducted.The clinicopathological data of 55 patients with low rectal cancer who underwent laparoscopic-assisted TaTME in the First Hospital of Jilin University from May 2017 to December 2018 were collected.There were 39 males and 16 females,aged (60-± 11) years,with a range from 24 to 80 years.Among the 55 patients,21 were in TNM stage Ⅰ,14 were in TNM stage Ⅱ,and 20 were in TNM stage Ⅲ;24 were in pathological stage T1-2 and 31 were in pathological stage T3.Observation indicators:(1) surgical and postoperative conditions;(2) follow-up;(3) analysis of influencing factors for postoperative defecation function.Follow-up was performed using questionnaires by telephone interview to detect the complications at 3 and 6 months after surgery up to June 2019.The measurement data with normal distribution were expressed as Mean± SD,and comparison between groups was done using the t test.Count data were expressed as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Univariate and multivariate analyses were performed using logistic regression models.Results (1) Surgical and postoperative conditions:55 patients successfully underwent laparoscopic-assisted TaTME without conversion to open surgery.The operation time,volume of intraoperative blood loss,diameter of postoperative pathological specimen,time to urinary catheter removal,distance between the anastomostic stoma and anal verge,and tumor diameter were (246±62) minutes,(69±27) mL,(3.5±0.7) cm,(2.1±0.9) days,(2.4±0.5) cm,and (3.9-± 1.6)cm,respectively.(2) Follow-up:55 patients were followed up at 3 months and 6 months after surgery,and the low anterior resection syndrome questionnaires were completed.Among the 55 patients,35 had low anterior resection syndrome at 3 months after surgery,and 24 had low anterior resection syndrome at 6 months after surgery,showing a significant difference (x2 =4.42,P＜0.05).There was no new onset low anterior resection syndrome in 55 patients after 3 months.(3) Analysis of influencing factors for defecation function:univariate analysis showed that the distance between the anastomotic stoma and anal verge and tumor diameter were influencing factors affecting defecation function of patients at 3 months after surgery (x2 =19.075,8.185,P＜ 0.05).The distance between the anastomotic stoma and anal verge was a influencing factor affecting the defecation function of patients at 6 months after surgery (x2=9.183,P＜0.05).Multivariate analysis showed that the distance between the anastomotic stoma and anal verge ＜ 2 cm,and tumor diameter ＞5 cm were independent risk factors affecting the defecation function of patients at 3 months after surgery (odds ratio =1.135,6.057,95％ confidence interval:1.089-1.323,1.206-30.435,P＜0.05).The distance between the anastomotic stoma and anal verge ＜ 2 cm was an independent risk factor affecting the defecation function of patients at 6 months after surgery (odds ratio =2.724,95％ confidence interval:1.982-3.066,P＜0.05).Conclusions The incidence of low anterior resection syndrome after laparoscopic-assisted TaTME for low rectal cancer is high.Distance between the anastomotic stoma and anal verge and tumor diameter are independent risk factors for the postoperative defecation founction.