Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl₄-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.
Animals ; Mice ; Gynostemma ; Liver Cirrhosis/drug therapy* ; Triterpenes/pharmacology* ; Ginsenosides ; Extracellular Matrix ; Dammaranes

Objective:To investigate the effects of IL-28B in a mouse model of dextran sulfate sodium (DSS)-induced colitis and to analyze the possible mechanism.Methods:Thirty-five male C57BL/6 mice were randomly divided into the following groups with seven mice in each group: control group, DSS group and three IL-28B groups (1.25 μg, 2.5 μg and 5 μg). The mice in the DSS group and IL-28B groups were fed with 2.5% DSS solution and from day 3, the IL-28B groups were given intraperitoneal injection of corresponding IL-28B every day and the DSS group was treated with PBS. During the experiment, the disease activity index (DAI) was evaluated daily. On day 8, the mice were sacrificed and peripheral blood, spleen, mesenteric lymph node and colon samples were collected. The colon samples were observed, measured in length and stained with HE, and histopathological scores were calculated based on HE staining. Changes of immune cells in different samples were detected by flow cytometry. ELISA was used to detect the expression of IL-12, IL-10, IL-1β, IL-6, IL-4 and IL-13 in serum and colon tissues.Results:Compared with the DSS group, the IL-28B group (2.5 μg) had lower DAI scores [(9.40±1.67) vs (3.50±1.73), P<0.01], less shortening of the colon [(5.16±0.61) cm vs (6.91±0.60) cm, P<0.01] and significantly lower histopathological scores [(7.33±0.58) vs (4.33±0.58), P<0.01]. Moreover, compared with the DSS group, the IL-28B group (2.5 μg) showed decreased macrophages in the peripheral blood [(21.39±3.21)% vs (15.63±2.98)%, P<0.05] and spleen [(3.03±0.28)% vs (2.05±0.48)%, P<0.05], and significantly increased mean fluorescence intensity of M2 macrophages in the colon [(1 361.00±293.40) vs (2 074.00±87.61), P<0.05]. IL-12 expression in colon tissues and IL-1β expression in serum were reduced, and IL-10, IL-4 and IL-13 expression in colon tissues was significantly increased in the IL-28B group (2.5 μg) as compared with those in the DSS group [IL-12: (31.72±6.92) pg/mg vs (5.41±3.41) pg/mg; IL-1β: (48.01±16.13) pg/ml vs (12.27±6.26) pg/ml; IL-10: (184.70±46.82) pg/mg vs (444.30±157.80) pg/mg; IL-4: (2.23±0.27) pg/mg vs (3.64±0.80) pg/mg; IL-13: (11.79±0.99) pg/mg vs (22.59±1.92) pg/mg; all P<0.05]. Conclusions:IL-28B might alleviate the severity of acute enteritis in mice by increasing the secretion of IL-4 and IL-13, regulating macrophage differentiation and modulating the expression of inflammatory factors.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Objective:To investigate the effect of head model in improving the photographic ability of interns during the photographic training of oral facial image in pediatric dentistry.Methods:A total of 60 interns of stomatology school affiliated to Xinjiang Medical University were randomly divided into head model training group, mutual training group and clinical probation group for photographic training. After the training, the interns in the three groups were evaluated for the photographic time, the level of photos, etc., by the training test and satisfaction level of volunteers. Besides, the head model training group was conducted by questionnaire survey. One-way analysis of variance and least significant difference analysis were used to analyze the data between groups by SPSS 17.0 software.Results:There was no statistical difference between the head model training group and the mutual training group in photographic time and level of photos, while both of them were much better in the head model training group and mutual training group than in the clinical probation group ( P<0.05). There was no statistical difference between the head model training group and the mutual training group in the satisfaction level, while that was lower in the head model training group than in the clinical probation group ( P<0.05). According to the questionnaire survey, most interns in the head model training group acknowledged its effects. Conclusion:The use of head model can help improve the oral photographic ability, and promote the teaching effect and efficiency in photographic training.

Objective:To investigate the best neutralization ratio of protamine and heparin during off-pump coronary artery bypass grafting(OPCABG) by analyzing the advantages and disadvantages of heparin residue after OPCABG.Methods:From July 2018 to January 2019, 112 patients undergoing elective OPCABG were included in this study. The patients’ whole blood was drawn at 2 time points, including before entering operating room and entering intensive care unit, to receive thrombelastography(TEG) and heparinase-modified thromboelastography(hmTEG) . Conventional coagulation indexes such as activated coagulation time(ACT) were also detected. All the patients were divided into 3 groups, the non-heparin residue group(30 cases), heparin residue group 1(42 cases) and heparin residue group 2(40 cases) according to the laboratory results of TEG, hmTEG and ACT. We observed the dosage of each group of protamine and heparin, as well as the ratio of heparin and protamine. The changes of R time in TEG and ACT between 3 groups were analyzed and compared. Postoperative chest tube drainage at postoperative 12 h and 48 h, cTnI peak value, incidence of perioperative myocardial infarction(MI), incidence of reoperation and poor wound healing, amount of blood loss and transfusion, and acute renal injury were compared between the 3 groups.Results:No significant trio-group differences existed in basic clinical characteristics(all P>0.05). Postoperative R(CKH)time was similar in the 3 groups( P>0.05). Comparing with heparin residue group 1 and heparin residue group 2, the ACT after protamine neutralizing heparin and postoperative R time were decreased, the dosage of protamine, ratio of heparin and protamine, cTnI peak value were increased in the non-heparin residue group( P<0.05). Comparing with heparin residue group 2, the dosage of heparin, postoperative chest tube drainage at postoperative 12h and 48h, amount of blood transfusion and transfusion probability were significantly decreased in non-heparin residue group( P<0.05), but compared with group 1 of heparin residue, there was no significant difference in the above indexes( P>0.05). The perioperative myocardial infarction, incidence of reoperation and poor wound healing, postoperative acute renal injury and time of in ICU stay showed no significant differences between the 3 groups( P>0.05). Conclusion:Moderate heparin residue after OPCAB suggests that it has myocardial protective effect, and does not significantly increase the risk of bleeding. A large number of heparin residues can affect the coagulation function and lead to bleeding tendency, increase the amount of blood loss and transfusion. It is reasonable to make ACT after protamine neutralize heparin higher than the level of ACT before operation, and not higher than 20% of the level before operation.

Objective:To explore the expression of serum miR-224-5p in PDAC and its significance for early clinical diagnosis.Methods:From August 2018 to April 2020, 40 patients with PDAC (11 patients with early PDAC, 29 patients with advanced PDAC), 21 patients with chronic pancreatitis and 40 healthy volunteer controls admitted in Qingdao Municipal Hospital were enrolled. The level of serum miR-224-5p in each group was detected by qRT-PCR method, and the correlation with clinicopathological parameters was analyzed. The receiver-operating characteristic (ROC) curve of miR-224-5p, CA19-9 and miR-224-5p combined with CA19-9 were drawn, and the sensitivity and specificity of the diagnosis were calculated.Results:The serum miR-224-5p levels in early PDAC group, middle and late PDAC group, chronic pancreatitis group and healthy control group were 3.21(2.01, 4.60), 4.70(3.50, 8.26), 1.72(1.02, 2.78) and 1.38(0.89, 2.11), respectively; and the level of serum miR-224-5p in the middle and late PDAC group was significantly higher than that in the early PDAC group, and that in the early PDAC group was significantly higher than that in the chronic pancreatitis group and the healthy control group, and all the differences were statistically significant ( P<0.05). The sensitivity of serum miR-224-5p combined with CA19-9, miR-224-5p, and CA19-9 in the diagnosis of overall PDAC was 95.0%, 85.0% and 67.5%, respectively; and the specificity was 70.0%, 82.5% and 87.5%, respectively. The sensitivity for early PDAC was 90.9%, 72.7% and 63.6%, and the specificity was 85.0%, 72.5% and 87.5%, respectively. MiR-224-5p combined with CA19-9 has the highest specificity in the diagnosis of PDAC. The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis (all P values <0.05). Conclusions:The expression of serum miR-224-5p was significantly up-regulated in patients with early PDAC, and The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis. The sensitity of serum miR-224-5p and miR-224-5p combined with CA19-9 for early PDAC diagnosis were superior to CA19-9 alone, which can be used as a potential sensitive biological marker for early screening of PDAC.

Objective    To explore the relationship between glycated hemoglobin (HbA1c) level and blood glucose fluctuations after coronary artery bypass grafting (CABG) and adverse events in non-diabetic patients, thus providing theoretical support for intensive preoperative blood glucose management in patients undergoing CABG surgery. Methods    A total of 304 patients undergoing CABG with or without valvular surgery from October 2013 to December 2017 were enrolled in this prospective, single-center, observational cohort study. We classified them into two different groups which were a low-level group and a high-level group according to the HbA1c level. There were 102 males and 37 females, aged 36–85 (61.5±9.5) years in the low-level group, and 118 males and 47 females aged 34–85 (63.1±9.4) years in the high-level group. The main results were different in hospital mortality and perioperative complications including in-hospital death, myocardial infarction, sternal incision infection, new stroke, new-onset renal failure and multiple organ failure. To assess the effects of confounding factors, multivariate logistic regression analysis was used. Results     Postoperative blood glucose fluctuation was more pronounced in the high-level group than that in the low-level group before admission [0.8 (0.6, 1.2) mmol/L vs. 1.0 (0.8, 1.8) mmol/L, P<0.01]. This study also suggested that the  incidence of major adverse events was significantly lower in the low-level group compared with the high-level group (P=0.001). Multivariate logistic regression analyses to correct the influence of other confounding factors showed that HbA1c (OR=2.773, P=0.002) and postoperative blood glucose fluctuations (OR=3.091, P<0.001) could still predict the occurrence of postoperative adverse events. Conclusion    HbA1c on admission can effectively predict blood glucose fluctuations in 24 hours after surgery. Secondly, HbA1c on admission and postoperative blood glucose fluctuations can further predict postoperative adverse events. It is suggested that we control the patient's preoperative HbA1c at a low level, which is beneficial to control postoperative blood glucose fluctuation and postoperative adverse events.