ObjectiveTo investigate the therapeutic effect of Bazhen Lihe Kangxian prescription on rats with liver fibrosis induced by carbon tetrachloride （CCl₄）， and to explore its mechanism of action against liver fibrosis. MethodsA total of 50 male Sprague-Dawley rats were randomly divided into blank group， model group， silybin group （43.19 mg/kg）， and low-， middle-， and high-dose Bazhen Lihe Kangxian prescription groups （7.96， 15.93， and 31.86 g/kg， respectively）. Subcutaneous injection of 40% CCl₄-olive oil solution （twice a week for 8 consecutive weeks） was performed to establish a model of liver fibrosis. After successful modeling， the rats in the blank group and the model group were given normal saline by gavage， while those in the treatment groups were given the corresponding drug by gavage， once a day for 4 consecutive weeks. HE staining and Masson staining were used to observe liver histopathological changes； an automatic biochemical analyzer was used to measure the serum levels of albumin （Alb）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）； ELISA was used to measure the serum levels of hyaluronic acid （HA）， collagen Ⅳ （Col-Ⅳ）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and laminin （LN）； Western blotting was used to measure the protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated PI3K （p-PI3K）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， mammalian target of rapamycin （mTOR）， and phosphorylated mTOR （p-mTOR） in liver tissue； RT-qPCR was used to measure the mRNA expression levels of collagen Ⅰ （Col-Ⅰ） and α-smooth muscle actin （α-SMA） in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group， the model group had disrupted hepatic lobular structure， disordered arrangement of hepatic cell cords， hepatocyte fatty degeneration， severe inflammatory cell infiltration， and deposition of massive blue collagen fibers， as well as significant increases in the levels of AST， ALT， HA， LN， Col‑Ⅳ， and PⅢNP and a significant reduction in the level of Alb （all P<0.01）. Compared with the model group， the silybin group and the three Bazhen Lihe Kangxian prescription groups had varying degrees of improvement in inflammatory cell infiltration， hepatocyte fatty degeneration， and collagen deposition in liver tissue， as well as significant reductions in the levels of AST， ALT， HA， LN， Col‑Ⅳ， and PⅢNP and a significant increase in the level of Alb （all P<0.01）. Compared with the blank group， the model group had significant increases in the protein expression levels of p‑PI3K/PI3K， p-Akt/Akt， and p‑mTOR/mTOR and the mRNA expression levels of Col-I and α-SMA in liver tissue （all P<0.01）； compared with the model group， the silybin group and the high- and middle-dose Bazhen Lihe Kangxian prescription groups had significant reductions in the protein expression levels of p-PI3K/PI3K （all P<0.01）， and the silybin group and the three Bazhen Lihe Kangxian prescription groups had significant reductions in the protein expression levels of p-Akt/Akt and p-mTOR/mTOR and the mRNA expression levels of Col-Ⅰ and α-SMA in liver tissue （all P<0.01）. ConclusionBazhen Lihe Kangxian prescription can improve CCl₄-induced liver fibrosis in rats and alleviate liver injury， possibly by inhibiting the PI3K/Akt/mTOR pathway.

Objective To investigate the association between brachial-ankle pulse wave velocity(baPWV)and left ventricular structure and function.Methods A total of 4864 participants who completed baPWV and transthoracic echocardiography from January 2010 to December 2021 were included.The participants were divided into three groups based on baPWV:Group T1:baPWV＜14m/s;Group T2:14m/s≤baPWV＜18m/s;Group T3:baPWV ≥18m/s.Multivariable Logistic regression and linear regression was used to examine the correlation between baPWV and interventricular septal thickness(IVS),left ventricular posterior wall thickness(LVPW),left ventricular end diastolic diameter(LVEDd),left ventricular mass index(LVMI),left ventricular ejection fraction(LVEF),and the presence of mitral e'/a'＜1.Results Increased baPWV was significantly associated with thickening of IVS(β=0.095,95％CI:0.007-0.182),thickening of LVPW(β=0.145,95％CI:0.056-0.233),and mitral e'/a'＜1(OR=2.200,95％CI:1.608-3.010)(P＜0.05).It was negatively correlated with LVEDd(β=-0.048,95％CI:-0.075--0.021)and showed no significant associa-tion with LVMI and LVEF(P＞0.05).Stratified analysis indicated that systolic blood pressure and baPWV had an interaction effect on LVEDd and mitral e'/a'＜1(P＜0.05).Conclusion BaPWV is associated with left ventricular remodeling and diastolic function.The correlation between baPWV and LVPW and LVEDd is stronger in groups with normal systolic blood pressure.In contrast,the correlation with mitral e'/a'＜1 is more prominent in groups with elevated systolic blood pressure.

Objective To explore the effective induction scheme for differentiation of adipose-derived mesenchymal stem cell (ADMSC) to insulin producing cell (IPC). Methods Different schemes of small molecule compound were used to induce the differentiation of ADMSC. The purity of cells was analyzed by flow cytometry and the morphological changes of cells were observed under the microscope. The quality, performance and insulin related indicators of cells were detected by hematoxylin-eosin and immunohistochemical staining. The maturity and activity of cells were detected by dithizone (DTZ) and diacetylfluorescein/propidium iodide staining. The induction effect of ADMSC differentiated into IPC was analyzed. Results The purity of ADMSC reached more than 99%, and the sphere forming properties of schemes Ⅰ, Ⅱ and Ⅲ were good. Cell induction mass, the expression effects of pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) and insulin and C peptide of schemes Ⅰ were both better than those of other schemes. The DTZ staining depth may be related to IPC maturity, among which the number of apoptotic cells in scheme Ⅰ was significantly less than that of scheme Ⅱ and Ⅲ. Conclusions Induction scheme Ⅰ may improve the differentiation efficiency of ADMSC to IPC and lay a certain foundation for future clinical IPC transplantation applications.

Objective To investigate the association between brachial-ankle pulse wave velocity(baPWV)and left ventricular structure and function.Methods A total of 4864 participants who completed baPWV and transthoracic echocardiography from January 2010 to December 2021 were included.The participants were divided into three groups based on baPWV:Group T1:baPWV＜14m/s;Group T2:14m/s≤baPWV＜18m/s;Group T3:baPWV ≥18m/s.Multivariable Logistic regression and linear regression was used to examine the correlation between baPWV and interventricular septal thickness(IVS),left ventricular posterior wall thickness(LVPW),left ventricular end diastolic diameter(LVEDd),left ventricular mass index(LVMI),left ventricular ejection fraction(LVEF),and the presence of mitral e'/a'＜1.Results Increased baPWV was significantly associated with thickening of IVS(β=0.095,95％CI:0.007-0.182),thickening of LVPW(β=0.145,95％CI:0.056-0.233),and mitral e'/a'＜1(OR=2.200,95％CI:1.608-3.010)(P＜0.05).It was negatively correlated with LVEDd(β=-0.048,95％CI:-0.075--0.021)and showed no significant associa-tion with LVMI and LVEF(P＞0.05).Stratified analysis indicated that systolic blood pressure and baPWV had an interaction effect on LVEDd and mitral e'/a'＜1(P＜0.05).Conclusion BaPWV is associated with left ventricular remodeling and diastolic function.The correlation between baPWV and LVPW and LVEDd is stronger in groups with normal systolic blood pressure.In contrast,the correlation with mitral e'/a'＜1 is more prominent in groups with elevated systolic blood pressure.

Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Objective To establish the patient derived xenograft ( PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B／c?nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B／c?nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high?throughput whole?genome exon sequencing were detected and recorded. Results The successful rate of established orthotopic PDX model of human PMP was 100%(10／10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity.The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells ( PMCA?S ), obvious tumor cell atypia and parenchymal invasion. Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX?2 and Ki?67 were positive, MUC6, CK7 and p53 were negative. Whole?exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c.1621A＞C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA?S is successfully established, which displays the characters of high?degree malignancy, high proliferation and strong aggressiveness.

Objective To establish the patient derived xenograft ( PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B／c?nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B／c?nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high?throughput whole?genome exon sequencing were detected and recorded. Results The successful rate of established orthotopic PDX model of human PMP was 100%(10／10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity.The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells ( PMCA?S ), obvious tumor cell atypia and parenchymal invasion. Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX?2 and Ki?67 were positive, MUC6, CK7 and p53 were negative. Whole?exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c.1621A＞C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA?S is successfully established, which displays the characters of high?degree malignancy, high proliferation and strong aggressiveness.

Objective To evaluate the extent and anatomic distribution of air trapping in lung in young asymptomatic female subjects to achieve early diagnosis of small airway diseases.Methods Fifty young females with normal pulmonary function were included retrospectively in this study.All subjects underwent both inspiratory and expiratory CT scans,the percentage of the area of air trapping(AT)and the percentage of the area of emphysema(Emph)were quantitatively analyzed.Comparison between bilateral lungs was analyzed using independent-samples t test;Comparisons among lobes were done using one-way ANOVA or Kruskal-Wallis rank sum test;Pairwise comparisons between lobes were conducted using LSD test or paired comparison;The effects of each lobe on AT were analyzed using Spearman's rank correlation coefficient,simple linear regression and multiple stepwise regression.Results There was a certain degree of air trapping in lung and a small amount of emphysema in young asymptomatic females.Air trapping was mainly located in the right middle lobe (RML)and bilateral upper lobes.The ratio of air trapping to volume was the highest in RML and the change of air trapping in the bilateral upper lobes had the greatest influence on the air trapping degree of the whole lung.Conclusion There is a certain degree of air trapping in lung in young asymptomatic females.The occurrence and development of air trapping in RML may be a sensitive biomarker for the early detection of pathophysiological changes in small airway diseases using imaging procedures.