[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.

[Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China].

Objective: To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors. Methods: This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels. Results: Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M (Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) (OR=1.23, 95%CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced (OR=0.68, 95%CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95%CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95%CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95%CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95%CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions: Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Does sinus membrane thickness influence the risk of perforation during lateral sinus lift surgery for dental implants? a systematic review and meta-analysis.

BACKGROUND: We reviewed the literature to examine if the thickness of the sinus membrane is a risk factor for perforation during lateral sinus lift surgery. MATERIAL AND METHODS: We searched Embase, PubMed, and Web of Science databases till 4th December 2023 for studies examining the risk of perforation with different sinus membrane thicknesses. Studies reporting sinus membrane thickness in perforation and non-perforation cases were also included. RESULTS: Eleven studies were eligible. All studies used cone beam computed tomography for measuring sinus membrane thickness. Meta-analysis showed that sinus membrane thickness was significantly lower in perforation cases as compared to non-perforation cases (MD: -0.91 95% CI: -1.48, -0.33 I2=94%). Four studies used 2mm as the cut-off to define thick and thin sinus membranes. Pooled analysis failed to demonstrate any significant difference in perforation rates (OR: 0.97 95% CI: 0.44, 2.17 I2=56%). Meta-analysis of studies using 1.5mm (OR: 0.66 95% CI: 0.29, 1.48 I2=72%) and 1mm cut-off (OR: 0.93 95% CI: 0.34, 2.56) also demonstrated similar non-significant results. CONCLUSIONS: Our study shows that the sinus membrane is significantly thinner in cases with perforations as compared to those with no perforations. However, a meta-analysis based on different membrane thickness cut-offs failed to demonstrate a relationship between thinner sinus membranes and a higher risk of perforation. There is a need for further studies examining the role of sinus membrane thickness on perforation rates.

[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.

[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 correlation between reflux esophagitis and Helicobacter pylori infection based on natural population].

Objective: Reflux esophagitis (RE) may be negatively correlated with Helicobacter pylori (H. pylori) infection, but the conclusion and relevant mechanism is still controversial. This study proposed to explore the correlation between RE and H. pylori infection based on natural population. Methods: From July 2013 to December 2014, 3 940 residents aged 40-69 years were recruited in Linqu County of Shandong Province and Hua County of Henan Province by the whole sampling method. All the subjects underwent gastroscopy, and gastric mucosa biopsy specimens were collected for pathological diagnosis and Warthin-Starry (WS) staining to identify H. pylori infection. Venous blood samples of some subjects were collected for H. pylori immunoglobulin G (H. pylori-IgG) detection. Also, demographic and sociological data were collected. Chi-square test and logistic regression were used to analyze the correlation between RE and H. pylori infection. Results: A total of 359 cases of RE were detected. Excluding RE and other upper gastrointestinal organic diseases, 3 382 cases were considered as controls. Chi-square test showed that WS staining positive rate in RE group was significantly lower than that in control group (P=0.023), but there was no significant difference in the positive rate of H. pylori-IgG between the two groups (P=0.281). There were significant differences between RE group and control group in gender composition, age, body mass index (BMI), smoking, alcohol consumption, education level and mucosal active inflammation. Multivariate regression analysis showed that RE was negatively correlated with gastric mucosa active inflammation [OR=0.754 (95%CI 0.600-0.949), P=0.016], and positively correlated with male [OR=4.231 (95%CI 3.263-5.486), P<0.001], age ≥60 years, BMI≥24 kg/m2 [OR=1.540 (95%CI 1.220-1.945), P<0.001]. Compared to those aged 40-49 years and 50-59 years, the odds ratio (OR) of RE in these aged ≥60 years were 1.566 (95%CI 1.144-2.143, P=0.005) and 1.405 (95%CI 1.093-1.805, P=0.008). Conclusion: RE is more closely related to H. pylori present infection. Multivariate analysis showed that RE is negatively correlated with active inflammation of gastric mucosa caused by H. pylori infection, and positively correlated with male, overweight and aged ≥60 years.

[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.

Chondroitin Sulfate Enhances Proliferation and Migration via Inducing ß-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes.

BACKGROUND: Chondroitin sulfate (CS) is found in humans' cartilage, bone, cornea, skin, and arterial wall. It consists of the foundation substance in the extracellular matrix (ECM) of connective tissue. The oral supplement form of CS is clinically used in treating osteoarthritis (OA). METHODS: Cell migration was observed by the transwell assay. The EMT, Akt/IKK/IκB pathways, TIMPs, collagen and MMPs in cell lysate were determined by Western blotting. The expression of MMP activity was determined by gelatin zymography. The production of reactive oxygen species (ROS) was determined by using a fluorescence spectrophotometer. RESULTS: In the current report, we demonstrated that CS can increase the cell proliferation and migration of chon-001 chondrocytes. Treatment with CS induced the epithelial-mesenchymal transition and increased the expression of type II collagen and TIMP-1/TIMP2 and inhibited the expressions and activities of metalloproteinase-9 (MMP-9) and metalloproteinase-2 (MMP-2). The phosphorylation of Akt, IκB kinase (IKK), IκB and p65 was decreased by CS. CS treatment resulted in ß-catenin production and XAV939, a ß-catenin inhibitor, and inhibited the cell proliferation by CS treatment. In addition, also significantly induced intracellular ROS generation. Treatment with antioxidant propyl gallate blocked cell migration induced by CS. CONCLUSION: We demonstrated that CS induced cell proliferation and migration of chondrocytes by inducing ß-catenin and enhancing ROS production. Moreover, our studies demonstrated that CS can increase the activity of chondrocytes and help patients with osteoarthritis to restore cartilage function.

[Application and outlook of robotics in prosthetic dentistry].

At present, robotic system has been applied in many aspects of the field of prosthetic dentistry, such as tooth preparation, oral implant surgery, full denture arrangement, prosthodontic material testing and robotic education of prosthodontics. The advantages of prosthodontic robotics lie in their ability to perform quantitative and precise operations whilerepeating the work flow indefinitely, which assist dentists to complete heavy and complicated daily treatment. In the research and development of prosthodontic robotics, the limitation of oral operation space should be fully considered, and robotics should have high safety and flexibility. The review briefly summarizes the application and existing problems of robotics in prosthodontics, and provides references for further development and design.

[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.

[Relationships between decreased LAMC3 and poor prognosis in ovarian cancer].

Objective: To investigate the correlations of laminin subunit gamma 3 (LAMC3) expression with prognosis of ovarian cancer (OC). Methods: LAMC3 protein expression was measured using immunohistochemical streptavidin-peroxidase-biotin connection method (IHC). Gene expression and related clinical data in the cancer genome atlas (TCGA) cohort and clinical proteomic tumor analysis consortium (CPTAC) were applied to analyse the correlation between gene and protein expressions and clinical outcomes. Correlations between LAMC3 and clinicopathological factors were evaluated using the Pearson χ2 test (2-sided). The probability of survival and significance was calculated using the Kaplan-Meier plot. The functional clustering of biological pathways enriched from co-expressed genes of LAMC3 was used to explore the possible mechanisms that LAMC3 might contribute to poor prognosis. Results: Based on the IHC results of 216 OC tissues or ovaries (including 208 tumors and 8 normal tissues) and 51 OC tissues (including 24 chemotherapy-resistant and 27 sensitive tissues), and the protein expression data from CPTAC (including 100 primary tumors and 25 normal tissues), the results showed that the protein expression of LAMC3 was significantly decreased in OC tissues compared with normal, decreased in advanced-stage tissues compared with early-stage tissues, and decreased in drug-resistant tissues compared with sensitive tissues (all P<0.05). Furthermore, low expression of LAMC3 protein was significantly associated with poor disease-free survival (DFS) and overall survival (OS) in 51 OC tissues (P<0.01), consistent with the results that the low levels of LAMC3 mRNA predicted short DFS and OS in 489 OC tissues of the TCGA cohort (P<0.05). The results suggested that low expression of LAMC3 might be the adverse factors for OC development, such as drug resistance and advanced tumors, and might be a risk indicator for prognosis. Moreover, functional clustering of biological pathways enriched from the co-expressed genes of LAMC3 in TCGA ovarian cohort indicated that LAMC3 potentially involved in regulation of OC via oncogene-pathways such as Ras associated protein 1 (Rap1), mitogen-activated protein kinase (MAPK), Ras and cell adhesion-related pathways such as extra cellular matrix (ECM)-receptor interaction and focal adhesion. It indicated that LAMC3 might contribute to short survival and tumor progression by regulation of the above pathways. Conclusion: Low expression of LAMC3 is related to poor prognosis and malignant progression in OC, and thus it is expected to be a new prognostic marker and therapeutic target for clinical treatment.

[Application and progress of artificial intelligence in endoscopic diagnosis of superficial esophageal cancer].

China is a country with high incidence of esophageal cancer. Advanced esophageal cancer not only brings serious threat to the health of patients, but also brings heavy economic burden to their families and society. Early diagnosis and treatment of esophageal cancer are always the hot spot in clinical research, and gastroscopy screening is the key point. The development of artificial intelligence is expected to provide new mean for early diagnosis and treatment of esophageal cancer in the aspects of endoscopy procedure and quality control.Through a brief overview of the concept and development of artificial intelligence in endoscopic diagnosis of superficial esophageal cancer, this study summarizes and reviews the research progress of artificial intelligence in the diagnosis of superficial esophageal carcinoma, and illustrates the importance of its application. This study also discusses the main problems and difficulties of artificial intelligence in the endoscopic diagnosis of esophageal carcinoma. It prospects the application of artificial intelligence in endoscopic esophageal diagnosis in the future.

[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.

The usefulness of non-invasive co-oximetry haemoglobin measurement for screening pre-operative anaemia.

Pre-operative anaemia (haemoglobin < 13.0 g.dl-1 ) is a modifiable peri-operative risk-factor. This is screened for using formal laboratory testing. A non-invasive finger-probe sensor that can accurately measure haemoglobin is a possible alternative. This study considers the accuracy of non-invasive haemoglobin measurement using the Rad-67™ Rainbow (Masimo Corp., Irvine, CA, USA) compared with formal laboratory testing and its usefulness in detecting pre-operative anaemia. A total of 392 patients had measurements taken for non-invasive haemoglobin and perfusion index values using the Rad-67 Rainbow, alongside further peri-operative parameters and a formal laboratory haemoglobin test. Bland-Altman and sensitivity analysis showed that the limits of agreement between non-invasive and formal laboratory haemoglobin testing were between -1.95 g.dl-1 and 2.23 g.dl-1 (p < 0.001). The overall performance of non-invasive haemoglobin measurement was better in men than women (ROC 91.1% vs. 78.2%) and less biased in men, mean -0.08 (SD 1.09, 95%Cl -0.23-0.07) compared with women (mean 0.38 (SD 0.99, 95%CI 0.24-0.52)). Pre-operative anaemia was more prevalent in women than men (50.3% vs. 14.4%). The sensitivity of non-invasive anaemia detection (haemoglobin < 13 g.dl-1 ) was 66% for women and 52% for men. A non-invasive haemoglobin value of 14.0 g.dl-1 had an overall 91% sensitivity for detecting pre-operative anaemia (82% in men and 93% in women). The Rad-67 Rainbow is inadequate for the estimation of formal laboratory haemoglobin and lacks sensitivity for detecting pre-operative anaemia, especially in women. Further advancement in technology and accuracy is needed before it can be recommended as a routine pre-operative screening test.

[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.

Quercetin protects human oral keratinocytes from lipopolysaccharide-induced injury by downregulating microRNA-22.

BACKGROUND: Quercetin exerts anti-inflammatory effects, but whether it can benefit patients with the chronic inflammatory disease of oral lichen planus (OLP), which is a common chronic mucocutaneous disorder with an immune-mediated pathogenesis, is unclear. The present research examined the impacts of quercetin in a cell-based OLP model in which human oral keratinocytes (HOKs) were treated with lipopolysaccharide (LPS). METHODS: Effects of quercetin on viability, proliferation, and apoptosis of HOKs were assessed using the Cell Counting Kit-8 assay, Western blotting, and flow cytometry, respectively. Effects of treatment on levels of microRNA-22 (miR-22) were measured using stem-loop reverse transcription polymerase chain reaction, while levels of proteins and phosphorylation in the PI3K/AKT and JAK1/STAT3 cascades were analyzed by Western blot. RESULTS: Quercetin mitigated LPS-induced reduction in HOK viability and elevation of apoptosis. It also weakened LPS-induced upregulation of miR-22. Quercetin treatment led to significantly higher levels of p-PI3K, p-AKT, p-JAK1, and p-STAT3. These effects of quercetin were enhanced when miR-22 was knocked down and partly reversed when miR-22 was overexpressed. CONCLUSION: Quercetin can mitigate LPS-induced injury in HOKs by downregulating miR-22, thereby activating PI3K/AKT and JAK1/STAT3 cascades.