[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[Clinical and genetic mutation characteristics of patients with primary hemophagocytic lymphohistiocytosis and their impact on prognosis].

Objective: To investigate the clinical and genetic mutation characteristics of patients with primary hemophagocytic lymphohistiocytosis (HLH) and their impact on prognosis. Methods: Sixty-three primary HLH patients with complete medical records admitted and diagnosed at Beijing Friendship Hospital of Capital Medical University from January 2013 to December 2022 were selected. The patients' clinical and laboratory features, genetic and rapid immunological indicator characteristics, treatment outcomes and prognosis were retrospectively analyzed. Follow-up was up to June 30, 2023, with a median follow-up time [M (Q1, Q3)] of 47 (21, 76) months. Overall survival was analyzed using Kaplan-Meier survival curve, and prognostic factors were analyzed using Cox proportional hazards regression model. Results: Sixty-three primary HLH patients included 35 males and 28 females, with a median age [M (Q1, Q3)] of 17 (7, 27) years. Clinical manifestations at the initial diagnosis mainly included fever (93.7%, 59/63), splenomegaly (87.3%, 55/63), hemophagocytosis (65.1%, 41/63), hepatomegaly (52.4%, 33/63) and central nervous system (CNS) involvement (38.1%, 24/63). A total of 39 patients (61.9%) were diagnosed with EB virus (EBV) infection at initial diagnosis.PRF1 and UNC13D gene mutations were the most common mutations, and the highest frequency mutation site in the PRF1 gene was c.1349C>T, and that of UNC13D gene was c.2588G>A. A total of 76.2% (48/63) of patients had reduced activity of natural killer (NK) cells. Cytotoxic cell degranulation function was impaired or absent in 52.7% (29/55) of patients, of which 79.2% (19/24) of patients with primary HLH with defects in degranulation-related genes had impaired degranulation function. The 1-year and 3-year overall survival rates were 74.8% and 66.7%, respectively. Cox multivariate analysis suggested that peripheral blood EBV≥10 000 copies/ml (HR=3.523, 95%CI: 1.418-8.757, P=0.007) was the risk factor for prognosis. Conclusions: The main clinical manifestations of primary HLH patients at the initial diagnosis include fever, splenomegaly, hemophagocytosis, hepatomegaly, and CNS involvement. PRF1 and UNC13D are the most commonly mutated genes. High copy number EBV infection in peripheral blood is the risk factor for prognosis.

[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

[Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation].

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/µl vs 852 cells/µl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.

[Maternal nutritional factors and environmental exposure in early life and childhood atopic dermatitis].

Atopic dermatitis(AD)is a chronic, recurrent, inflammatory skin disease in children. The disease is characterized by dryness, chronic eczema-like lesions and obvious itching, seriously affecting the quality of life of children and their families. The pathogenesis of AD is not yet to be clear, and it might be the interaction of genetic susceptibility and environmental exposure to induce skin barrier impairment and immune system dysfunction. In recent years, the role of maternal factors or intrauterine environment exposure on childhood allergic diseases has been attracted attention, and the hypothesis that allergic diseases originate from the fetal period has been postulated. Maternal exposures called "early life exposure", such as nutritional factors during pregnancy (folate, vitamin D, vitamin E and polyunsaturated fatty acid) and tobacco exposure, home environmental exposure may be related with childhood atopic dermatitis. This article would focus on the recent research about maternal nutritional factors and family environmental exposure during pregnancy on offspring's atopic dermatitis.

[Endoscopic hand-suturing combined with titanium clips for rectal defects closure after endoscopic submucosal dissection: a pilot study].

Objective: To explore the feasibility of endoscopic hand-suturing (EHS) for rectal defects closure after endoscopic submucosal dissection (ESD), and the clinical practicability of EHS combined with titanium clips. Methods: This is a prospective study performed by two experienced endoscopists from the Cancer Hospital, Chinese Academy of Medical Sciences who had received EHS training in sixporcine gastric ESD defects in vivo before the study. From December 2022 to February 2022, 20 patients with rectal mucosal lesions or submucosal diseases underwent ESD. Then EHS combined with titanium clips was adopted to close the rectal ESD defects. Specifically, we first sutured the defects as much as possible through EHS, then use titanium clips to fix the tail of the suture, and finally use additional titanium clips to close the residual parts of the defects that cannot be sutured. The main observational indicators were complete closure of the wound and delayed bleeding within one month after surgery. Results: In the 20 rectal cases, the size of defects ranged from 2.2 to 3.6 cm, with a median of 2.7 cm. All cases achieved complete closure without delayed bleeding, of which 12 (60.0%) were completely sutured with EHS and 8 (40.0%) required additional titanium clips to achieve complete closure after suturing. Conclusion: EHS technique is feasible and safe for rectum. EHS combined with titanium clips can also effectively close the rectal ESD defects, prevent postoperative delayed bleeding, and may be easier to be implemented in clinical practice.

[Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor].

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

[Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer].

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 µm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 µm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

[Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion].

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

[The clinical value of multi-target stool fecal immunochemical test-DNA in early screening and diagnosis for colorectal cancer].

Objective: To investigate the clinical diagnostic value of multi-target stool fecal immunochemical test-DNA (FIT-DNA) test in colorectal cancer (CRC) and advanced adenoma (AA). Methods: A total of 235 patients who were undergoing colonoscopy or colorectal cancer surgery in the Cancer Hospital, Chinese Academy of Medical Sciences from April 2021 to January 2022 were prospectively enrolled. There were 141 males and 94 females, with an average age of (55±13) years (22-86). The patients were divided into two groups, including 215 patients who were first diagnosed but not treated (86 cases of CRC, 12 cases of AA, 25 cases of non-advanced adenoma, 8 cases of hyperplastic or other polyps and 84 apparently healthy cases) and 20 patients in the intervention group (2 cases with a history of CRC surgery, 6 cases with a history of endoscopic surgery, 4 non-CRC patients with special diseases and 8 cases with a history of neoadjuvant chemoradiotherapy). Fresh stool samples were collected before intestinal preparation or surgery for FIT-DNA test using the matching kit for sample processing and nucleic acid purification. KRAS mutation and methylation of BMP3 and NDRG4 genes were detected by fluorescence probe method, and FIT method was employed to detect fecal occult blood. Colonoscopy or pathological biopsy results were used as the gold standard. And the screening and diagnostic efficacy of FIT-DNA test for colorectal cancer and advanced adenoma were evaluated by receiver operating curve (ROC). Results: The sensitivity of FIT-DNA test for early colorectal cancer and advanced adenoma was 7/7 and 8/12, respectively. And the negative predictive value was 98.1% (104/106) and 93.7% (104/111), respectively. The overall screening sensitivity for both early colorectal cancer and advanced adenoma was 15/19, and the negative predictive value was 96.3% (104/108). Besides, the area under the curves (AUCs) were 0.982 (95%CI: 0.960-1.000, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.841 (95%CI: 0.724-0.957, P<0.05), respectively. Moreover, the diagnostic sensitivity of FIT-DNA test was 98.8% (85/86) for colorectal cancer, 8/12 for advanced adenoma, and 94.9% (93/98) for both colorectal cancer and advanced adenoma, with a specificity of 88.9% (104/117). The AUCs were 0.968 (95%CI: 0.937-0.997, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.942 (95%CI: 0.905-0.979, P<0.05), respectively. After the inclusion of intervention group, the overall diagnostic sensitivity and specificity of FIT-DNA test was 91.6% (98/107) and 89.1% (114/128), respectively. Conclusion: FIT-DNA test has a high early screening and diagnostic efficacy for colorectal cancer.

[Characteristics of N6-methyladenosine modification patterns in t(8;21) acute myeloid leukemia].

OBJECTIVE: To investigate the relationship between AML1-ETO (AE) fusion gene and intracellular N6-methyladenosine (m6A) modification pattern in t(8;21) acute myeloid leukemia (AML). METHODS: RNA m6A sequencing was performed in SKNO-1 and AE knockdown SKNO-1 (SKNO-1 siAE) cells using RNA-protein co-immunoprecipitation and high-throughput sequencing (methylated RNA immunoprecipitation sequencing, MeRIP-Seq) to analyze the changes in m6A modification of the entire transcriptome. Transcriptome sequencing (RNA-seq) was performed using high-throughput sequencing. The differentially modified mRNAs were further functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The changes in m6A-related enzyme expressions were detected using real-time PCR. RESULTS: A total of 26 441 genes were identified in AE knockdown AML cells and AE-expressing cells, containing 72 036 m6A peaks. AE knockdown caused a reduction of the number of intracellular m6A peaks from 37 042 to 34 994, among which 1278 m6A peaks were significantly elevated and 1225 were significantly decreased; 1316 genes with newly emerged m6A modification were detected and 1830 genes lost m6A modification after AE knockdown. The differential peaks were mainly enriched in pathways involving cancer and human T-lymphocytic leukemia virus I. RNA-seq results showed that 2483 genes were up-regulated and 3913 genes were down-regulated after AE knockdown. The combined analysis of MeRIP-Seq and RNA-Seq results revealed relatively high expression levels of m6A-modified genes as compared with the genes without m6A modification (SKNO-1: 0.6116±1.263 vs 2.010±1.655, P < 0.0001; SKNO-1 siAE: 0.5528±1.257 vs 2.067±1.686, P < 0.0001). The m6A modified genes located in the 3'UTR or 5 'UTR had significantly higher expression levels than those located in exonic regions (SKNO-1: 2.177± 1.633 vs 1.333 ± 1.470 vs 2.449 ± 1.651, P < 0.0001; SKNO-1 siAE: 2.304 ± 1.671 vs 1.336 ± 1.522 vs 2.394 ± 1.649, P < 0.05). Analysis of RNA-seq data identified 3 m6A-related enzymes that showed significantly elevated mRNA expression after AE knockdown, namely WTAP, METTL14, and ALKBH5 (P < 0.05), but the results of real-time PCR showed that the expressions of WTAP and ALKBH5 were significantly increased while the expression of METTL14 was lowered after AE knockdown (P < 0.05). CONCLUSION: AE knockdown results in differential expressions of m6A-associated enzymes, suggesting that the AE fusion gene regulates the expression of one or more m6A-associated enzymes to control cellular methylation levels.

[Association of skin lesion severity with clinical features of psoriatic arthritis].

Objective: To investigate the relationship between psoriasis severity and clinical features in psoriatic arthritis (PsA). Methods: Patients were recruited from the Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021, and data were collected including the baseline demographic characteristics, various clinical manifestations (including arthritis, nail disease, comorbidities), laboratory tests[including erythrocyte sedimentation rate(ESR), C-reactive protein (CRP)], health assessment questionnaire (HAQ). Body surface area (BSA) and psoriasis area and severity index (PASI) were selected for the tools of assessment of cutaneous psoriasis. Patients were divided to two groups, including the severe psoriasis group (BSA>10%) and the non-severe psoriasis group (BSA≤10%). Disease assessment included ankylosing spondylitis disease activity score (ASDAS), disease activity score 28 (DAS28) and disease activity in psoriatic arthritis (DAPSA). Results: 1 074 eligible patients with PsA were recruited, and 106 (9.9%) had severe psoriasis. Compared with non-severe psoriasis group, the severe psoriasis group had more peripheral joint involvement (including patients with ever or current peripheral arthritis, 94.3% vs. 85.6%), more polyarticular joint involvement (including patients with current peripheral arthritis, 74.0% vs. 58.2%), more axial joint involvement (51.4% vs. 39.9%), more nail disease (72.6% vs. 61.4%), more frequency of smoking (20.2% vs. 18.7%), and higher proportion of hypertension (23.4% vs. 14.4%). In addition, the severe psoriasis group had higher level of ESR [33(10, 70) mm/1h vs. 20(9, 38) mm/1h] and CRP [18.6(5.0, 60.8) mg/L vs. 7.0(2.4, 18.1) mg/L], higher values of DAS28-ESR (4.5±1.7 vs. 3.7±1.5), DAS28-CRP (4.2±1.5 vs. 3.4±1.4), ASDAS-ESR (3.5±1.4 vs. 2.6±1.2), and ASDAS-CRP(3.4±1.6 vs. 2.5±1.2), higher scores of HAQ [0.6(0.1, 1.0) vs. 0.3(0.0, 0.8)]. Conclusion: Patients with PsA with severe psoriasis bore a heavier disease burden. Therefore, clinicians were supposed to pay more attention to them. In addition to skin lesions, they should also focus on examination of other clinical manifestations, such as joints and nails.

[Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure].

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

[Effect of ruxolitinib combined with glucocorticoid on cytomegalovirus activation in acute graft-versus-host disease].

Objective: To observe the effect of ruxolitinib combined with glucocorticoid on cytomegalovirus (CMV) activation in patients with acute graft-versus-host disease (aGVHD) . Methods: The clinical data of 195 patients who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from August 2018 to September 2020 were retrospectively analyzed. According to the severity of aGVHD, the patients were divided into the non-GVHD group, aGVHD grade Ⅰ group, aGVHD grade Ⅱ-Ⅳ group, and aGVHD grade Ⅲ/Ⅳ group. In addition, they were classified into two subgroups according to the first-line treatment regimen for aGVHD: combined regimen group (ruxolitinib combined with glucocorticoid) and classical regimen group (glucocorticoid alone) . The cumulative incidence of CMV activation, the duration of CMV activation, and the duration of CMV negativity in each subgroup at 90 and 180 days after transplantation were analyzed. The overall survival and disease-free survival rates of patients in both regimens were compared. Results: Sixty-four (32.8%) patients in the group did not develop aGVHD. The numbers of patients with grade Ⅰ, Ⅱ-Ⅳ, and Ⅲ/Ⅳ aGVHD were 30 (15.4%) , 101 (51.8%) , and 14 (7.2%) , respectively. Compared with patients in the classical regimen, no significant difference was observed in the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity in patients with grade Ⅰ-Ⅳ aGVHD in the combined regimen at 90 and 180 days after transplantation (P>0.05) . Further analysis of patients with grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD showed that the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity did not show significant difference between the two treatment regimens (P>0.05) . In addition, there was no significant difference in the overall survival and disease-free survival rates of patients in both regimens (P>0.05) . Conclusion: Ruxolitinib combined with glucocorticoid as the first-line therapy for aGVHD did not increase the risk of CMV activation.

[Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm].

Objective: To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions. Methods: The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding. Results: A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group (P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm (OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion (OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions: The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

[Comparison of long-term outcomes between endoscopic submucosal dissection and surgical resection for early gastric cancer with undifferentiated histology].

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.

[Efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms].

Objective: To discuss the efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms. Methods: The clinical-pathological data of 21 patients who were admitted to the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences and underwent endoscopic papillectomy of major duodenal papilla neoplasms from January 2014 to January 2020 were retrospectively studied, their postoperative outcomes and complication were also analyzed. Results: Tweenty-one patients were successfully performed endoscopic papillectomy of major duodenal papilla neoplasms. The resected lesions varied between 0.5-2.8 cm. Completed lesion was resected in 19 cases and lesion blocks in 2 cases. The incidence of postoperative complication was 52.4% (11/21), including 8 cases of postoperative bleeding (38.1%). Five patients stopped bleeding after endoscopic hemostasis and 3 patients stopped after interventional embolization. Two patients experienced perforation (9.5%) and recovered after conservative treatment including anti-inflammatory treatment and abdominal drainage. Five patients had pancreatitis (23.8%) and recovered after treatment with pre-somatostatin and anti-inflammatory rectal suppository. Preoperative pathological results of 21 patients suggested that 11 were high-grade intraepithelial neoplasia and 8 were low-grade intraepithelial neoplasia, and 2 were chronic inflammation. Postoperative pathological results suggested that 4 were adenocarcinoma, and the rest 17 were adenoma. The coincidence rate of preoperative biopsy results and postoperative pathology was 38.1%(8/21), and underestimate of the pathological stage occurred in 11 patients (52.4%) during the preoperative biopsy, overestimate occurred in two patients (9.5%). Four cases had a positive incisal margin. All patients had good prognoses and no death event occurred during the follow-up period. Conclusions: Early-stage major duodenal papilla neoplasms should be treated with aggressive resection. Endoscopic papillectomy of duodenal papilla neoplasms is safe, effective, and can be recommended as the preferred procedure for major duodenal papilla neoplasms.

[Clinicopathological features of the colorectal serrated adenoma and analysis on influencing factors of malignancy].

Objective: Serrated adenoma is recognized as a precancerous lesion of colorectal cancer, and the serrated pathway is considered as an important pathway that can independently develop into colorectal cancer. However, little is known about the related risk factors of carcinogenesis of serrated adenoma. The purpose of this study was to analyze the distribution characteristics and potential malignant factors of serrated adenoma in the colon and rectum. Methods: A retrospective case-control study was conducted to collect the clinical data of patients with serrated adenoma who underwent colonoscopy and were pathologically diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2017 to July 2019, and exclude patients with two or more pathological types of lesions. The clinical characteristics of serrated adenoma were summarized, and univariate and logistic multivariate regression analysis was conducted to explore the influencing factors for serrated adenoma to develop malignant transformation. Results: Among 28 730 patients undergoing colonoscopy, 311 (1.08%) were found with 372 serrated adenomas, among which 22 (5.9%) were sessile serrated adenomas/polyps, 84 (22.6%) were traditional serrated adenomas, and 266 (71.5%) were unclassified serrated adenomas according to WHO classification. The pathological results showed that 106 (28.5%) lesions were non-dysplasia, 228 (61.3%) lesions were low grade intraepithelial neoplasia, and 38 (10.2%) lesions were high grade intraepithelial neoplasia or cancer. There were 204 (54.8%) lesions with long-axis diameter <10 mm and 168 (45.2%) lesions with length long-axis ≥ 10 mm. 238 (64.0%) lesions were found in the left side colon and rectum and 134 (36.0%) lesions in the right side colon. Gross classification under endoscopy: 16 flat type lesions (4.3%), 174 sessile lesions (46.8%), 117 semi-pedunculated lesions (31.5%), 59 pedunculated lesions (15.9%). Narrow-band imaging international colorectal endoscopic (NICE) classification: 85 (22.8%) type I lesions, 280 (75.3%) type II lesions, 4 (1.1%) type III lesions. Univariate analysis showed that lesion size, lesion location, lesion site and different WHO classifications were associated with malignant transformation of colorectal serrated adenoma (all P<0.05). For the serrated adenomas with different NICE classifications, there were statistically significant differences in the distribution of malignant lesions among groups (P=0.001). Multivariate analysis showed that the long-axis diameter of the lesion ≥10 mm (OR=6.699, 95% CI: 2.843-15.786) and the lesion locating in the left side colorectum (OR=2.657, 95% CI: 1.042-6.775) were independent risk factors for malignant transformation. Conclusions: Serrated adenomas mainly locate in the left side colon and rectum, and are prone to malignant transformation when the lesions are ≥10 mm in long-axis diameter or left-sided.

[Clinical outcomes of endoscopic piecemeal mucosal resection for superficial esophageal carcinoma and precancerous lesions].

Objective: To explore the short and long-term outcomes of endoscopic piecemeal mucosal resection including endoscopic mucosal resection (EMR) and multiband mucosectomy (MBM) for superficial esophageal carcinoma and precancerous lesions, and analyze the risk factors for prognosis. Methods: From March 1 2001 to May 31 2017, 371 patients with 416 lesions who were diagnosed as superficial esophageal carcinoma or high-grade intraepithelial neoplasm and underwent EMR or MBM were retrospectively enrolled in this study. Long-term recurrence free survival (RFS) rate and the risk factors, including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, for the long-term outcome were also analyzed. Results: The incidence of complication was 17.1% in the EMR group and 17.4% in the MBM group, without significant difference (P=1.000). The median follow-up period was 70.6 months. The 5-years RFS was 93.9% and 10-years RFS was 87.8%, respectively. Local recurrence was found in 2 cases in each group and they were curatively treated by endoscopic submucosal dissection. Heterogeneous multiple primary esophageal cancer was diagnosed in 5 and 3 cases for the EMR and MBM group, of whom 5 cases were curatively treated with endoscopic resection. Other 3 cases were diagnosed with advanced esophageal cancer, of whom 2 patients died. Lymph node metastasis (LNM) was found in 5 cases in the EMR group and 4 cases in the MBM group, of whom 6 patients died. Distant metastasis was found in 5 cases in the EMR group and 3 cases in the MBM group, of whom 5 patients died. There were 83 patients combined with risk factors including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, of whom 8 patients were diagnosed as LNM and 8 patients as distant metastasis. The 5-years RFS of patients with 1, 2, and 3 risk factors were 93.6%, 82.2%, and 25.0%, and the difference was statistically significant (P<0.001). Conclusions: EMR and MBM are both safe and feasible procedures for superficial esophageal carcinoma and precancerous lesions. Additional treatments should be selected according to the variety of risk factors to acquire better long-term outcome and life quality.

[Therapeutic effect of endoscopic submucosal dissection on the treatment of early gastric cancer].

Objective: To analyze the long-term therapeutic effect of endoscopic submucosal dissection (ESD) on the treatment of early gastric cancer (EGC). Methods: We retrospectively reviewed EGC patients who underwent ESD at Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), from January 2009 to December 2016. The incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were analyzed. Kaplan-Meier method was used to analyze 5-years recurrence free survival (RFS) and 5-years disease special survival (DSS) of all patients. Results: A total of 255 EGC patients were enrolled in this study, included 175 differentiated early gastric cancer (D-EGC) patients and 80 undifferentiated early gastric cancer (UD-EGC) patients. Among them, 171 patients within the extended indication of ESD while 84 patients beyond the extended indication of ESD. Among the 225 patients, the incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were 2.0%, 2.0% and 2.4%, respectively. The local recurrence rates of D-EGC group and UD-EGC group was 1.7% and 2.5%, respectively, without significant difference (χ(2)=0.176, P=0.675). The incidence rates of synchronous and heterogenous cancer in the D-EGC group were 2.3% and 3.4%, higher than 1.2% and 0 of UD-EGC group, although there was no significant difference (χ(2)=0.306, P=0.580 vs χ(2)=2.809, P=0.094). There were no significant differences in 5-years RFS (91.3% vs 95.9%, P=0.236) and 5-years DSS (100% vs 98.6%, P=0.156) between D-EGC group and UD-EGC group. Conclusions: The long-term outcome of ESD in the treatment of EGS is good. More attention should be paid to the occurrence of local recurrence and heterogeneous cancer in EGC patients undergo ESD. These patients still have a good long-tern outcome even undergoing ESD for more than once.