Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95％CI:1.05～1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95％CI:1.02～1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.

Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95％CI:1.05～1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95％CI:1.02～1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.

Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.

Objective:To explore the diagnostic efficacy of methylene blue staining combined with light transmission method (termed as light transmission and staining) in endoscopic submucosal dissection (ESD) specimens of early gastric cancer.Methods:A retrospective study was conducted on 75 specimens of early gastric cancer treated with ESD at Beijing Friendship Hospital, Capital Medical University from October 2021 to August 2023. Under a stereomicroscope, magnified observation and transmitted light transmission and staining observation were performed to compare the demarcation line (DL), irregular microvascular pattern (IMVP) and irregular microsurface pattern (IMSP) of the lesion, and the differences among histological types were compared. Furthermore, the false positive rate of surgical margin, the detection rate of undifferentiated cancer and multifocal lesions were compared against the 88 controls processed by traditional method.Results:Using the light transmission and staining method, DL, IMVP and IMSP were detected in 96.0% (72/75), 89.3% (67/75), and 98.7% (74/75), which was higher than 72.0% (54/75), 6.7% (5/75), and 26.7% (20/75) by using the magnified observation ( χ 2=8.036, P<0.001; χ 2=0.640, P<0.001; χ 2=0.369, P<0.001). There was no statistical difference in the coincidence rate of endoscopy and pathology between differentiated type, undifferentiated type and mixed type [92.2% (59/64), 50.0% (1/2), 77.8% (7/9), χ 2=5.145, P=0.055]. Compared to traditional methods, light transmission and staining could increase the detection rate of undifferentiated cancer [14.7% (11/75) VS 4.5% (4/88), χ 2=4.964, P=0.026] and reduce the false positive rate of surgical margins [1.3% (1/75) VS 11.4% (10/88), χ 2=4.585, P=0.032], but showed no statistical difference in the detection rate of multifocal lesions [5.3% (4/75) VS 0.0% (0/88), χ 2=2.841, P=0.094]. Conclusion:Light transmission and staining enhances pathological recognition of DL, IMVP and IMSP during specimen processing, improving detection of undifferentiated cancer and reducing false positive of margin.

Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.

Objective:To explore the diagnostic efficacy of methylene blue staining combined with light transmission method (termed as light transmission and staining) in endoscopic submucosal dissection (ESD) specimens of early gastric cancer.Methods:A retrospective study was conducted on 75 specimens of early gastric cancer treated with ESD at Beijing Friendship Hospital, Capital Medical University from October 2021 to August 2023. Under a stereomicroscope, magnified observation and transmitted light transmission and staining observation were performed to compare the demarcation line (DL), irregular microvascular pattern (IMVP) and irregular microsurface pattern (IMSP) of the lesion, and the differences among histological types were compared. Furthermore, the false positive rate of surgical margin, the detection rate of undifferentiated cancer and multifocal lesions were compared against the 88 controls processed by traditional method.Results:Using the light transmission and staining method, DL, IMVP and IMSP were detected in 96.0% (72/75), 89.3% (67/75), and 98.7% (74/75), which was higher than 72.0% (54/75), 6.7% (5/75), and 26.7% (20/75) by using the magnified observation ( χ 2=8.036, P<0.001; χ 2=0.640, P<0.001; χ 2=0.369, P<0.001). There was no statistical difference in the coincidence rate of endoscopy and pathology between differentiated type, undifferentiated type and mixed type [92.2% (59/64), 50.0% (1/2), 77.8% (7/9), χ 2=5.145, P=0.055]. Compared to traditional methods, light transmission and staining could increase the detection rate of undifferentiated cancer [14.7% (11/75) VS 4.5% (4/88), χ 2=4.964, P=0.026] and reduce the false positive rate of surgical margins [1.3% (1/75) VS 11.4% (10/88), χ 2=4.585, P=0.032], but showed no statistical difference in the detection rate of multifocal lesions [5.3% (4/75) VS 0.0% (0/88), χ 2=2.841, P=0.094]. Conclusion:Light transmission and staining enhances pathological recognition of DL, IMVP and IMSP during specimen processing, improving detection of undifferentiated cancer and reducing false positive of margin.

Objective:To investigate the diagnostic value of conventional endoscopy (CE) and endoscopic ultrasonography (EUS) for invasion depth prediction of superficial gastric cancer.Methods:A total of 84 patients with superficial gastric cancer underwent both CE and EUS before treatment at Beijing Shijitan Hospital from January 2011 to December 2019. The patients were divided into CE affirmation group (47 cases) and CE non-affirmation group (37 cases) according to the endoscopist′s affirmation in the results of CE. Diagnostic accuracy of each method was compared with the histology of the resected specimen. And influential factors for the diagnosis were analyzed.Results:The overall accuracy in determining the invasion depth of superficial gastric cancer was 73.8% (62/84) for CE and 81.0% (68/84) for EUS respectively ( P=0.092). In CE affirmation group, the diagnostic accuracy of CE was significantly higher than that in the CE non-affirmation group [93.6% (44/47) VS 48.7% (18/37), χ2=21.656, P<0.001]. Twenty (23.8%) of 84 lesions were over-staged by CE, dignosed as surgical candidates, and 8 (40.0%) of the over-staged diagnosis were modified by additional EUS assessment. Multivariate logistic analysis showed that influential factors associated with observer affirmation included uneven surface of lesion ( OR=5.076, 95% CI: 1.628-15.821, P=0.005), margin elevation ( OR=3.831, 95% CI: 1.238-11.857, P=0.020) and undifferentiated carcinoma ( OR=6.887, 95% CI: 1.882-25.204, P=0.004). Conclusion:For patients of CE affirmation in the invasion depth, the diagnostic accuracy is high. For those of non-affirmation, additional EUS can improve the diagnostic accuracy and help to develop a more appropriate regime.