BACKGROUND:It has been elucidated that downregulation of nuclear enriched abundant transcript 1(NEAT1)inhibits the progression of keloid fibroblasts,but the exact mechanism is not fully understood. OBJECTIVE:To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1(lncRNA NEAT1)on the proliferation,apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4(USP4)axis. METHODS:Keloid fibroblasts were divided into five groups:si-NC group,control check group,si-NEAT1 group,si-NEAT1+miR-136-5p inhibitor group,and si-NEAT1+inhibitor-NC group.qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p;cell counting kit-8 assay and EDU staining were performed to measure cell proliferation;flow cytometry was performed to measure apoptosis;scratch-healing experiment was performed to measure cell migration;western blot assay was performed to measure the protein expressions of USP4,p27,Bax,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain;dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. RESULTS AND CONCLUSION:Compared with the si-NC group,the NEAT1 expression,absorbance value at 450 nm,percentage of EDU positive cells,scratch-healing rate,the protein expressions of USP4,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain decreased in the si-NEAT1 group(P<0.05),while the expression of miR-136-5p,apoptosis rate,and the protein expressions of p27 and Bax increased(P<0.05).miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts.There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4.To conclude,silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis..

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Helicobacter pylori (Hp) is a unipolar, microaerobic, multiflagellar, spiral-shaped Gram-negative bacterium that survives and colonizes human gastric mucosa. As a classⅠcarcinogen associated with gastric cancer, long-term stimulation of gastric mucosa by Hp can cause atrophic gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It has been reported that Hp can cause epithelial-mesenchymal transition (EMT) in gastric epithelial cells, thereby inducing gastric cancer. We review the mechanism of Hp-induced EMT in gastric epithelial cells, in order to provide new insights for early diagnosis and targeted therapy of gastric cancer.

  Objective  To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance.  Methods  Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve.  Results  A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall.  Conclusions  A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Objective:To investigate the incidence and mortality of gynecological tumors in China from 1990 to 2019, and explore the impact of age, period and birth cohort on the incidence and mortality of gynecological tumors, and predict the incidence and mortality trends of gynecological tumors, so as to provide references for formulating the prevention and control strategies of gynecological tumors.Methods:Based on the Global Burden of Disease Study 2019 (GBD 2019) database, the Joinpoint regression model was used to analyze the change trends of standardized incidence rates and mortality rates of cervical cancer, uterine cancer and ovarian cancer in China. The age, period and cohort effects of the incidence and mortality of 3 gynecological tumors were analyzed by using R software based on age-period-cohort model. The grey forecast model (GM) (1, 1) was used to fit the trends of incidence rates and mortality rates of 3 gynecological tumors, and predict the incidence rates and mortality rates from 2020 to 2034.Results:From 1990 to 2019, the standardized incidence rates of cervical cancer, uterine cancer and ovarian cancer showed upward trends in China, the standardized incidence rates increased from 8.41/100 000, 5.13/100 000 and 2.56/100 000 in 1990 to 11.01/100 000, 6.39/100 000 and 4.54/100 000 in 2019, the average annual percent changes (AAPC) were 0.9 % (95% CI: 0.8%-1.1%), 0.8 % (95% CI: 0.6%-1.0%) and 2.0 % (95% CI: 1.9%-2.1%), respectively, and the differences were statistically significant (all P < 0.001). The standardized mortality rate of ovarian cancer showed an increasing trend year by year, the standardized mortality rate increased from 1.76/100 000 in 1990 to 2.77/100 000 in 2019, with the AAPC of 1.6 % (95% CI: 1.4%-1.7%), while the standardized mortality rates of uterine cancer and cervical cancer showed decreasing trends year by year, the standardized mortality rates decreased from 2.38/100 000 and 5.85/100 000 in 1990 to 1.17/100 000 and 5.13/100 000 in 2019, with the AAPC of -2.4 % (95% CI: -2.6% - -2.3%) and -0.4 % (95% CI: -1.6% - -0.3%), respectively, and the differences were statistically significant (both P < 0.001).The analysis of age effect showed that the incidence rates and mortality rates of cervical cancer, uterine cancer and ovarian cancer showed gradual upward trends with age, reaching a peak in the ≥85 years old group. The analysis of period effect showed that the incidence risk of cervical cancer and uterine cancer decreased firstly, then increased and then decreased, and the incidence risk of cervical cancer and uterine cancer was the highest in 1990-1994 ( RR = 1.04, 95% CI: 0.86-1.27) and 2005-2009 ( RR = 1.08, 95% CI: 0.88-1.31), respectively. The incidence risk of ovarian cancer increased firstly and then decreased, and the incidence risk of ovarian cancer was the highest in 2000-2004 ( RR = 0.96, 95% CI: 0.71-1.30). The mortality risk of cervical cancer showed a trend of decreasing firstly, then increased and then decreased, and the mortality risk was the highest in 1990-1994 ( RR = 1.22, 95% CI: 0.86-1.27). The mortality risk of uterine cancer showed a trend of decreasing year by year, and the mortality risk was the highest in 1990-1994 ( RR = 1.26, 95% CI: 0.85-1.87). The mortality risk of ovarian cancer showed a trend of increasing firstly and then decreased, and the mortality risk was the highest in 1990-1994 ( RR = 1.01, 95% CI: 0.69-1.48). Cohort effect analysis showed that the risk of incidence and mortality of cervical cancer, uterine cancer and ovarian cancer showed a gradually decreasing trend except for a small fluctuation in individual birth cohorts, but the birth cohort 1990-1994 showed a rebound trend. The GM results showed that the overall incidence rates of cervical cancer, uterine cancer and ovarian cancer in China were increased year by year. In addition to the mortality rate of uterine cancer at a stable level, the mortality rates of cervical cancer and ovarian cancer showed upward trends. Conclusions:The disease burden of gynecological tumors in China is still heavy. Age, period and birth cohort effects affect the incidence and mortality of cervical cancer, uterine cancer and ovarian cancer to varying degrees.

Ulcerative colitis is a common disease of the digestive system in China,which seriously affects the quality of life of patients due to its disease characteristics,such as easy recurrence,repeated course of disease and carcinogenic tendency.Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are considered as new inflammatory biomarkers,which have been found to be related with ulcerative colitis.This article reviewed the clinical value of NLR and PLR in ulcerative colitis.