Objective To detect the expression level of 4-aminobutyrate aminotransferase(ABAT)in bone marrow of patients with myelodysplastic syndrome(MDS),and analyze its influence on clinicopathological features and prognosis of patients.Methods From January 2016 to March 2020,92 patients with MDS and 30 patients with acute myeloid leukemia(AML)from the First Affiliated Hospital of Xingtai Medical College were retrospectively collected.Meanwhile,30 patients with immunothrombocytopenia who did not develop MDS or other clonal diseases of the blood system during a 3-year follow-up were collected as control group.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the relative expression level and methylation level of ABAT mRNA of all patients,and the relative expression level and methylation level of ABAT mRNA among different clinical characteristics of MDS patients were compared.Multivariate logistic regression analysis was used to analyze the risk factors affecting the adverse prognosis of MDS.The clinical value of detecting ABAT methylation level in predicting poor prognosis of MDS patients was analyzed by receiver operating characteristic(ROC)curve.Kaplan-Meier method was used to calculate the 3-year survival rate between groups with different ABAT mRNA relative expression levels and methylation levels,and log-rank test was used for their comparison.Results The expression level of ABAT mRNA in MDS group(0.42±0.08)was lower than that in control group(0.56±0.15)and AML group(0.52±0.10),while the methylation level of ABAT(32.51±5.32)was higher than that of AML group(26.21±4.58)and control group(10.25±4.31),and the differences were significant(t=4.251,4.562;10.415,8.326,all P<0.001).The methylation level of ABAT in high-risk patients(42.65±5.32)was higher than that in low-risk patients(25.63±4.16),intermediate-risk-1 patients(30.59±2.51)and intermediate-risk-2 patients(33.25±3.69)by IPSS risk grade,and the differences were significant(t=8.329,7.077,15.874,all P<0.001).Poor Karyotype analysis result[OR(95%CI):4.973(1.524～8.581),P=0.004],high IPSS risk grade[OR(95%CI):8.542(2.365～14.521),P<0.001]and ABAT hypermethylation level[OR(95%CI):6.178(1.589～13.021),P<0.001]were the risk factors affecting the poor prognosis of MDS.The cut-offvalue of ABAT methylation level to predict the poor prognosis of MDS were 30.54,and the area under the curve(AUC),the sensitivity and specificity were 0.92,0.874 and 0.851,respectively.The 3-year survival rate of the high ABAT methylation group(>30.54)was 66.67%,which was lower than that of the low ABAT methylation group(≤30.54)was 93.18%,with significant difference(Log-rank x2=9.814,P=0.002).Conclusion The ABAT methylation levels in MDS bone marrow increase,which is a risk factor affecting the poor prognosis of patients.ABAT basal level>30.54 is expected to become a factors predicting the poor prognosis of patients.

Objective:To develop a prototype artificial intelligence immunofluorescence image recognition system for classification of antinuclear antibodies in order to meet the growing clinical requirements for an automatic readout and classification of immunof luorescence patterns for antinuclear antibody (ANA) images.Methods:Immunofluorescence images with positive results of ANA in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 2020 to December 2021 were collected. Three senior technicians independently and in parallel interpreted the Immunofluorescence images to determine the ANA results. Then the images were labeled according to the ANA International Consensus on Fluorescence Patterns (ICAP) classification criteria. There were 7 labeled groups: Fine speckled, Coarse speckled, Homogeneous, nucleolar, Centromere, Nuclear dots and Nuclear envelope. Each group was randomly divided into training dataset and validation dataset at a ratio of 9∶1 by using random number table. On the deep learning framework PyTORCH 1.7, the convolutional neural network (CNN) training platform was constructed based on ResNet-34 image classification network, and the automatic ANA recognition system was established. After the model was established, the test set was set up separately, the judgment results of the model were output by ranking the prediction probability, with the results of the 2 senior technicians was taken as "golden standard". Parameters such as accuracy, precision, recall and F1-score were used as indicators to evaluate the performance of the model.Results:A total of 23138 immunofluorescence images were obtained after segmentation and annotation. A total of 7 models were trained, and the effects of different algorithms, image processing and enhancement methods on the model were compared. The ResNet-34 model with the highest accuracy andswas selected as the final model, with the classification accuracy of 93.31%, precision rate of 91%, and recall rate of 90% and F1-score of 91% in the test set. The overall coincidence rate between the model and manual interpretation was 90.05%, and the accuracy of recognition of nucleolus was the highest, with the coincidence rate reaching 100% in the test set.Conclusion:The current AI system developed based on deep learning of the ANA immunofluorescence images in the present study showed the ability to recognize ANA pattern, especially in the common, typical, simple pattern.

Background: Patients with dyspepsia are the major group of outpatient department of gastroenterology. Dyspeptic symptoms are closely related to anxiety and/or depression. However, the relationship of anxiety and/or depression to dyspeptic symptoms in outpatients undergoing gastroscopy is still unclear. Aims: To investigate the incidence of anxiety and/or depression in outpatients undergoing gastroscopy and its correlation with the severity of dyspepsia. Methods: Outpatients underwent gastroscopy from November 2021 to December 2021 at West China Hospital, Sichuan University were recruited. Generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression, respectively. Rome diagnostic questionnaire for functional gastrointestinal disorders, severity of dyspepsia assessment questionnaire, visceral sensitivity index were used to evaluate dyspepsia. The correlation of anxiety and/or depression with dyspepsia was analyzed. Results: A total of 458 questionnaires were collected effectively, including 146 (31.9%) patients with anxiety and/or depression. Compared with the non-anxiety and depression group, the number of gastroscopy in the anxiety and/or depression group was significantly higher (P<0.05). Compared with the non-anxiety and depression group, the incidences of extremely mild/mild dyspepsia, moderate/severe epigastric fullness, postprandial fullness, epigastric pain and belching were significantly increased in the anxiety and/or depression group (P<0.05). Anxiety and/or depression was significantly correlated with the severity of dyspepsia and visceral sensitivity (r=0.421, r=0.143; P< 0.05). Conclusions: Anxiety and/or depression is common in outpatients undergoing gastroscopy; anxiety and/or depression may lead to repeated endoscopic examinations; anxiety and/or depression is significantly correlated with dyspepsia and visceral sensitivity.

Esophageal cancer (EC) is one of the most common cancers with high morbidity and mortality rates. EC includes two histological subtypes, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC primarily occurs in East Asia, whereas EAC occurs in Western countries. The currently available treatment strategies for EC include surgery, chemotherapy, radiation therapy, molecular targeted therapy, and combinations thereof. However, the prognosis remains poor, and the overall five-year survival rate is very low. Therefore, achieving the goal of effective treatment remains challenging. In this review, we discuss the latest developments in chemotherapy and molecular targeted therapy for EC, and comprehensively analyze the application prospects and existing problems of immunotherapy. Collectively, this review aims to provide a better understanding of the currently available drugs through in-depth analysis, promote the development of new therapeutic agents, and eventually improve the treatment outcomes of patients with EC.

Objectives:To examine the efficacy of terminal branches portal vein embolization(TBPVE) for the increment of FLR in hepatocellular carcinoma (HCC) patients and to introduce its clinical value with transcatheter chemoembolization(TACE) in the treatment of HCC patients without surgery.Methods:One hundred and fifty HCC patients from three clinical centers of china underwent TBPVE technique from December 2016 to May 2021,including 89 males and 61 females. The average age was 51.9 years(range:18 to 79 years).One hundred and one patients were diagnosed with a background of HBV infection,including 27 patients with portal venous hypertension.TACE was performed simultaneously with TBPVE in 102 patients.Fifty-three patients underwent hepatectomy,who were subdivided into HBV positive and HBV negative groups,with TACE and without TACE groups to analyze the increment of future liver remnant (FLR), complications and survival data.These data were also analyzed in other 97 patients without hepatectomy.Results:All the patients reached adequate FLR successfully in 14 days after TBPVE including patients with portal venous hypertension.The average increment rates of FLR was 56.2% in 7 days and 57.8% in 14 days after TBPVE. There was no significant difference neither between HBV positive and HBV negative groups(7 days:(55.0±27.3)% vs.(57.8±20.9)%, t=0.885, P=0.373; 14 days:(57.3±24.6)% vs.(58.3±23.7)%; t=0.801, P=0.447),or between with TACE and without TACE groups(7 days:(62.3±26.3)% vs. (48.8±20.6)%; t=1.788, P=0.077;14 days:(64.4±25.0)% vs.(55.2±23.1)%; t=1.097, P=0.257).The morbidity and mortality rates were 20.8% and 1.9% in patients with hepatectomy.The 1-,3-year overall survival(OS) and disease-free(DFS) rates were 87.5%,64.5% and 64.7%,40.6% for patients underwent surgery.There was no significant difference of 1-,3-year OS and DFS between HBV positive and negative groups,but there were different between TACE and without TACE groups.The 1-,3-year OS for patients underwent TBPVE and TACE but without surgery were 80.1%, 53.7%. Conclusion:TBPVE is a good alternative technique for modulation of FLR for staged hepatectomy even in HBV positive HCC patients and can be applied with TACE procedure simultaneously as an option treatment for patients with no intend to surgery.

Objective:To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC).Methods:A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher′s exact test was used to analyze the gene mutation differences between groups.Results:After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group ( P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients ( P<0.05). Conclusions:CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

Objectives:To examine the efficacy of terminal branches portal vein embolization(TBPVE) for the increment of FLR in hepatocellular carcinoma (HCC) patients and to introduce its clinical value with transcatheter chemoembolization(TACE) in the treatment of HCC patients without surgery.Methods:One hundred and fifty HCC patients from three clinical centers of china underwent TBPVE technique from December 2016 to May 2021,including 89 males and 61 females. The average age was 51.9 years(range:18 to 79 years).One hundred and one patients were diagnosed with a background of HBV infection,including 27 patients with portal venous hypertension.TACE was performed simultaneously with TBPVE in 102 patients.Fifty-three patients underwent hepatectomy,who were subdivided into HBV positive and HBV negative groups,with TACE and without TACE groups to analyze the increment of future liver remnant (FLR), complications and survival data.These data were also analyzed in other 97 patients without hepatectomy.Results:All the patients reached adequate FLR successfully in 14 days after TBPVE including patients with portal venous hypertension.The average increment rates of FLR was 56.2% in 7 days and 57.8% in 14 days after TBPVE. There was no significant difference neither between HBV positive and HBV negative groups(7 days:(55.0±27.3)% vs.(57.8±20.9)%, t=0.885, P=0.373; 14 days:(57.3±24.6)% vs.(58.3±23.7)%; t=0.801, P=0.447),or between with TACE and without TACE groups(7 days:(62.3±26.3)% vs. (48.8±20.6)%; t=1.788, P=0.077;14 days:(64.4±25.0)% vs.(55.2±23.1)%; t=1.097, P=0.257).The morbidity and mortality rates were 20.8% and 1.9% in patients with hepatectomy.The 1-,3-year overall survival(OS) and disease-free(DFS) rates were 87.5%,64.5% and 64.7%,40.6% for patients underwent surgery.There was no significant difference of 1-,3-year OS and DFS between HBV positive and negative groups,but there were different between TACE and without TACE groups.The 1-,3-year OS for patients underwent TBPVE and TACE but without surgery were 80.1%, 53.7%. Conclusion:TBPVE is a good alternative technique for modulation of FLR for staged hepatectomy even in HBV positive HCC patients and can be applied with TACE procedure simultaneously as an option treatment for patients with no intend to surgery.

Objective:To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC).Methods:A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher′s exact test was used to analyze the gene mutation differences between groups.Results:After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group ( P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients ( P<0.05). Conclusions:CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

OBJECTIVE: To investigate the effects of manganese(Mn) and high fat diet(HFD) co-exposure on the neurological behavior and gut microbiota in mice, and to observe the correlation between them. METHODS: Specific pathogen free adult male C57 BL/6 mice were randomly divided into 4 groups. Mice in control group and Mn exposure group were fed with normal diet, while the HFD group and co-exposure group were fed with HFD. Both the Mn exposure group and the co-exposure group were exposed to 10 mg/(kg·d) manganese chloride by intraperitoneal injection, while the control group and HFD group were treated with 0.9% sodium chloride solution of the same volume, once per day for 60 consecutive days. At the end of exposure, the mice were subjected to experiments of neurological behaviors. Then, the mice were sacrificed and intestinal feces were collected. The relative abundance of gut microbiota(relative abundance>1.000%) was detected by high-throughput sequencing. RESULTS: After exposure, the body weight of the HFD group and the co-exposure group increased significantly(P<0.05), while that of the Mn exposure group decreased(P<0.05), compared with the control group. The latency, time in central, crossing, total distance and open arm time(OT%) of mice in the Mn exposure group were lower than that of the control group(P<0.05), and close arm time(CT%) prolonged(P<0.05). Compared with the control group and the HFD group, the latency, rearing, time in central, crossing, total distance, OT% and open arm entry(OE%) of mice in the co-exposure group decreased(P<0.05), and CT% increased(P<0.05). The total distance of mice in the co-exposure group was lower than that of the Mn exposure group(P<0.05). The relative abundance of Firmicutes increased(P<0.05), those of Bacteroidetes and Actinobacteria decreased in mice in the HFD group at the phylum level(P<0.05) compared with mice in the control group. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria increased(P<0.05), and Bacteroidetes and Actinobacteria decreased(P<0.05) in mice in the Mn exposure group. The relative abundance of Oscillospira, Bacteroides and Prevotella of mice in the HFD group reduced at the genus level(P<0.05) compared with the control group. The relative abundance of Lactobacillus increased in Mn exposure group(P<0.05), and Oscillospira, Bacteroides and Prevotella decreased(P<0.05). The relative abundance of Firmicutes, Cyanobacteria and Lactobacillus of mice in the co-exposure group increased(P<0.05), and those of the remaining 6 bacteria were lower(P<0.05) compared with mice in the other 3 groups. Among the mice of co-exposure group, the latency was positively correlated with Bacteroidetes(P<0.05). The rearing was positively correlated with Firmicutes(P<0.05) and negatively correlated with Actinobacteria(P<0.01). The OE% was negatively correlated with Firmicutes(P<0.05) and positively correlated with Actinobacteria(P<0.05). The crossing was positively correlated with Prevotella(P<0.05). CONCLUSION: Manganese combined with HFD had a synergistic effect on the abnormality of neurological behavior of mice. There are some correlation between the abnormality of neurological behavior and the homeostatic imbalance of intestinal flora in mice.

In order to facilitate the treatment strategies for biliary tract injury, hilar cholangiocarcinoma, bile duct tumor thrombus, cholangiocellular carcinoma and bile duct cystic dilatation, many classifications have been made, even more than 10 types for one disease. Each type is represented by numbers or English alphabet, which are not only confusing but also difficult to remember. The Academician Mengchao Wu divided the liver into five sections and four segments base on its anatomy, this classification is very direct and visual, thus had been using till now. In order to overcome those complicated problems, it is considered to develop a new classification based on actual anatomic location similar to that for liver cancer, which is easy to remember and to directly determine the treatment strategy. All kinds of classifications have their own characteristics and advantages and disadvantages. This practical classifications avoid the complexity and may be useful for clinicians.