Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.

Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.

Objective To investigate the relationships of the expression of microRNA-487a-3p (miR-487a-3p) and A kinase-interacting protein 1 (AKIP1) mRNA in the endometrial cancer (EC) tissue with the patient survival within 5 years after surgery. Methods The EC tissue and adjacent normal tissue samples were collected from 130 EC patients who underwent surgical treatment at the Fourth Hospital of Shijiazhuang from September 2016 to April 2019.qRT-PCR was employed to determine the expression levels of miR-487a-3p and AKIP1 mRNA.The patients were followed up for 5 years after surgery to record the survival status.After removal of the patients who missed follow-up,78 surviving patients were recorded as the EC survival group,and 34 deceased patients were recorded as the EC death group.The dual luciferase reporter gene assay was conducted to verify the targeting relationship between miR-487a-3p and AKIP1 mRNA.Comparison was conducted for the expression levels of miR-487a-3p and AKIP1 mRNA between adjacent normal tissue and EC tissue,the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue among patients with different clinical pathological parameters,and the clinical pathological parameters and the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue between the EC survival group and the EC death group.The correlations of miR-487a-3p and AKIP1 mRNA levels in the EC tissue with the degree of tumor differentiation,International Federation of Gynecology and Obstetrics (FIGO) stage,lymph node metastasis,and depth of muscle invasion were analyzed.The relationships of miR-487a-3p and AKIP1 mRNA with patient prognosis and the risk factors affecting the survival of EC patients within 5 years after surgery were analyzed to evaluate the value of miR-487a-3p and AKIP1 mRNA levels in predicting the survival of EC patients within 5 years after survival. Results The EC tissue showed lower miR-487a-3p level (0.41±0.08 vs. 1.00±0.05;t=71.306,P<0.001) and higher AKIP1 mRNA level (2.35±0.37 vs. 1.00±0.03;t=41.465,P<0.001) than the adjacent normal tissue.The miR-487a-3p low expression group and AKIP1 mRNA high expression group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer than the miR-487a-3p high expression group and AKIP1 mRNA low expression group,respectively (all P<0.05).The results of dual luciferase reporter gene assay showed that the relative activity of luciferase in the miR-487a-3p small interfering RNA (siRNA)+AKIP1 mRNA-wild type (WT) group was higher than that in the miR-487a-3p empty vector+AKIP1 mRNA-WT group (2.85±0.19 vs. 1.00±0.04;t=23.339,P<0.001).There was no significant difference in the relative activity of luciferase between the miR-487a-3p empty vector+AKIP1 mRNA-mutant type (MUT) group and the miR-487a-3p siRNA+AKIP1 mRNA-MUT group (1.04±0.05 vs. 1.05±0.03;t=0.420,P=0.683).MiR-487a-3p in the EC tissue had negative correlations with AKIP1 mRNA,FIGO stage,lymph node metastasis,and depth of muscle invasion and a positive correlation with the degree of tumor differentiation (all P<0.001).AKIP1 mRNA had positive correlations with FIGO stage,lymph node metastasis,and depth of muscle invasion and a negative correlation with the degree of tumor differentiation (all P<0.001).The 5-year overall survival rates in the miR-487a-3p high expression group and AKIP1 mRNA low expression group (89.47% and 84.91%) were higher than those in the miR-487a-3p low expression group and AKIP1 mRNA high expression group (49.09% and 55.93%),respectively (both P<0.05).The EC death group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer,higher AKIP1 mRNA level in the EC tissue,and lower miR-487a-3p level than the EC survival group (all P<0.05).Low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,deep invasion of muscle layer,low miR-487a-3p level,and high AKIP1 mRNA level were independent risk factors for the survival of EC patients within 5 years after surgery (all P<0.05).The area under curve (AUC) values of miR-487a-3p and AKIP1 mRNA alone (0.785 and 0.789,respectively) were lower than that of their combination (0.908) in predicting the survival of EC patients within 5 years after surgery (both P<0.05). Conclusion The EC tissue has a low miR-487a-3p level and a high AKIP1 mRNA level,both of which are correlated with clinicopathological parameters and prognosis and can be used to predict the survival of EC patients within 5 years after surgery.
Humans ; Female ; Endometrial Neoplasms/pathology* ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Middle Aged ; Survival Rate ; Nuclear Proteins

Objective:To analyze and compare the differences of expression profiles between RPL and normal adipose tissue by transcriptome sequencing(RNA-Seq),then identify the key genes related to prognosis and explore their potential mechanisms.Methods:Tumor tissues and normal adipose tissues of patients with RPL were collected for RNA-Seq,and then the differentially ex-pressed genes were analyzed by GO and KEGG enrichment analysis.Based on TCGA,the high-risk genes related to prognosis were screened and verified by Kaplan-Meier curve and receiver operat-ing characteristic(ROC)curve.Results:Compared with normal adipose tissue,279 differentially expressed genes were simultaneously up-regulated in RPL tissues,which were mainly enriched in immune response and PPAR signaling pathway.Combined with TCGA,7 stable prognostic high risk genes were identified and the overall survival rate of the high risk group was significantly lower than that of the low risk group(P＜0.05).Conclusion:KCNQ5,RBPJ and some other genes may be re-lated to the poor prognosis of RPL patients.The analysis of the mechanism of these genes in RPL is expected to provide new evidence for the formulation of diagnosis and treatment strategies for RPL patients.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

Objective To investigate the importance of a nomogram model based on biomarkers and CT signs in the prediction of the invasive risk of ground glass nodules. Methods A total of 322 patients with ground glass nodule, including 240 and 82 patients in the model and verification groups, respectively, were retrospectively analyzed. Independent risk factors for the invasive risk of ground glass nodules were screened out after using single and multiple Logistic analysis. R software was used to construct the nomogram model, and clinical decision curve analysis (DCA), receiver operating curve (ROC), and calibration curve were used for internal and external verification of the model. Results In this study, the independent risk factors for the invasive risk of ground glass nodules included systemic immune-inflammation index (SII), CYFRA21-1, edge, vascular cluster sign, and nodular consolidation tumor ratio (CTR). The area under the ROC curve of the constructed nomogram model had a value of 0.946, and that of the external validation group reached 0.932, which suggests the good capability of the model in predicting the invasive risk of ground glass nodules. The model was internally verified through drawing of calibration curves of Bootstrap 1000 automatic sampling. The results showed that the consistency index between the model and actual curves reached 0.955, with a small absolute error and good fit. The DCA curve revealed a good clinical practicability. In addition, nodule margin, vascular cluster sign, and CTR were correlated with the grade of pathological subtype of invasive adenocarcinoma. Conclusion A nomogram model based on biomarkers and CT signs has good value and clinical practicability in the prediction of the invasive risk of ground glass nodules.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor of the digestive system, characterized by rapid progression and difficulties of early diagnosis. Five-year survival rate of the patients is less than 9%. With the acceleration of global population aging and lifestyle change, the incidence of PDAC has been increasing annually. Currently, surgical treatment and chemotherapy remain the standard treatment options for PDAC patients. Early symptoms of PDAC are so undetectable that most patients miss the optimal opportunity for radical surgical resection. Even among those who undergo surgery, the high recurrence rate remains a major problem. PDAC is known for its unique tumor microenvironment. The cellular and non-cellular components in the tumor microenvironment account for as much as 90% of the tumor stroma, presenting many potential targets for PDAC therapy. Activated pancreatic stellate cells within PDAC tissue express specific proteins and secrete various cytokines and metabolites, which directly contribute to the proliferation, invasion, and metastasis of PDAC cells. These elements are critical in extracellular matrix production, connective tissue hyperplasia, immune tolerance, and drug resistance. Immune cells, such as macrophages and neutrophils, exert immunosuppressive and tumor-promoting roles in PDAC progression. The extracellular matrix, which serve as a natural physical barrier, induces interstitial hypertension and reduces blood supply, thereby hindering the delivery of drugs to the tumor. Additionally, it helps the metastasis and differentiation of PDAC cells, reducing the efficacy of clinical chemotherapy and immunotherapy. Although chemotherapeutic agents like gemcitabine have been used in the clinical treatment of PDAC for more than 20 years, the curative effect is obstructed by their poor stability in the bloodstream, low cellular uptake, and poor targeting. While small-molecule inhibitors targeting mutations such as KRAS^G12C, BRCA, and NTRK fusion have shown great potential for molecular targeted treatments and gene therapies of PDAC, their broader application is limited by side effects and restricted scope of patients. The advancement of nanotechnology brings new strategies for PDAC treatment. By virtue of unique size characteristics and actual versatility, different drug-delivery nanosystems contribute to overcome the dense stromal barrier, prolong the circulation time of therapeutics and realize precise PDAC treatment by targeted drug delivery. Clinical nanodrugs such as albumin-bound paclitaxel (nab-paclitaxel) and irinotecan liposome greatly improve the pharmacokinetics of conventional chemotherapeutics and promote drug accumulation inside the tumor, thereby are applying to the first-line treatment of PDAC. It is noteworthy that none nanodrugs with active targeting design have been approved for clinical treatment yet, though many are in clinical trials. In this review, we discuss promising targeting strategies based on different nanodrug delivery systems for treatment of PDAC. One major nanostrategy focuses on the tumor cell targeting and its applications in chemotherapy, molecular targeting therapy, gene therapy, and immunotherapy of PDAC. Another nanostrategy targets the tumor microenvironment, which highlights the nanosystems specifically regulating pancreatic stellate cells, immune cells and the extracellular matrix. Recent progress of developing new nanotheraputics for breakthrough in the fight of PDAC are elaborated in this review. We also provide our perspectives on the challenges and opportunities in the field.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:To investigate the clinical efficacy and safety of heat-clearing and spleen-invigorating method in the treatment of Helicobacter pylori (Hp) initial treatment failure population.Methods:The clinical data of 155 patients with initial Hp failure in our hospital from January 2021 to December 2022 were retrospectively analyzed. According to the treatment plan, they were divided into TCM group (66 cases) and Western medicine group (89 cases). Python 3.70 was used for bias score matching (PSM) to obtain samples with balanced covariates between groups. Finally 66 pair of cases were successfully matched according to the propensity score and the 1:1 matching principle.The TCM group was given Yiqing Capsule + Jianpi Pills (4 weeks) as a course of treatment. The Western medicine group was given four anti-Hp remedial regimen, 2 weeks for 1 course. 2 groups were treated for 1 course. Hp was detected by 14C breath test and its clearance rate was calculated. The overall symptoms of functional dyspepsia (FD) were evaluated from four aspects: postprandial fullness, early satiety, middle and upper abdominal pain, and middle and upper abdominal burning sensation. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:After treatment, the Hp clearance rate was 75.76% (50/66) in the TCM group and 83.33% (55/66) in the Western medicine group, which was significantly improved compared with that before treatment, without statistical significance ( χ2=1.16, P=0.281). After treatment, the scores of fullness and discomfort after meal [1 (0,2) vs. (2,4), Z=-6.85], early satiety [2 (0,2) vs. 4 (4, 6), Z=-8.02], middle and upper abdominal pain [2 (2, 4) vs. 4 (4, 6), Z=-4.48] in the TCM group were lower than those in Western medicine group ( P<0.01). The total effective rate was 75.76% (50/66) in the TCM group and 69.70% (46/66) in the Western medicine group, without statistical significance ( χ2=2.00, P=0.573). No adverse reactions occurred in the 2 groups during treatment. Conclusion:In terms of heat-clearing and spleen-invigorating method for Hp initially failed patients, its Hp clearance rate and clinical total effective rate are comparable to Western medicine, and can effectively improve the clinical symptoms of patients with Hp initial treatment failure.