Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

Triterpenoid saponins is an important secondary metabolites in medicinal plants, and the tetracyclic triterpenoid saponins, as one of the main categories, have very high medicinal value and market demand. However, there is no systematic review on the research. Thus, the elucidation of the biosynthetic pathway and metabolism of the medicinal plant tetracyclic triterpenoid saponins has important theoretical significance and broad application prospects.In this review, the biosynthetic pathway and metabolic regulation of medicinal plant of tetracyclic triterpenoid saponins were discussed. My focus in this paper was to introduce the research development of several metabolic biosynthetic pathways of tetracyclic triterpenoid saponins centered on dammarane type, and the gene improvement by methods such as metabolic pathway and other technological methods. This study provides references on secondary metabolic framework of medicinal plants of tetracyclic triterpenoid saponins, accurately locating secondary metabolism and its key enzymes, and promoting the sustainable uses of medicinal plant resources.

Objective: To study the correlation between the level of serum Chitinase-3-like protein 1 (CHI3L1) and the significant liver fibrosis and liver cirrhosis in patients with chronic liver disease, and to evaluate its diagnostic value. Methods: 165 patients with chronic liver disease were selected, liver histopathological examination was performed to detect serum CHI3L1 concentration. Four indexes of hepatic fibrosis (type III procollagen, collagen IV, laminin, hyaluronic acid), aspartate aminotransferase/platelet ratio index (APRI) and FIB-4 (fibrosis- 4) scores were based on the pathological findings of liver biopsy and compared the advantages and disadvantages of serum CHI3L1 with other methods for the diagnosis of hepatic fibrosis and liver cirrhosis. A multivariate regression analysis model was created, and receiver operating characteristic curve was analyzed. Results: The level of serum CHI3L1 increased with increase of fibrosis stage and was highest in liver cirrhosis stage. In the period of S0 to 1, the levels of S2 to 3 and S4 were 62.82 (41.40 ~ 87.20), 70.94 (48.47 to 122.60) and 141.06 (78.18 ~ 197.40), and there were statistically significant differences between the groups (P < 0.001). The area under the curve for the diagnosis of significant liver fibrosis was 0.68 (0.60 to 0.77), and 0.74 (0.65 to 0.83) for cirrhosis in CHI3L1. Multivariate regression analysis showed that CHI3L1 was an independent predictor of significant fibrosis and cirrhosis. The combined diagnostic model based on CHI3L1, collagen IV and FIB-4 scores further improved the diagnostic value. The area under the curve for the diagnosis of significant fibrosis and cirrhosis was 0.79 (0.72 to 0.86) and 0.80 (0.73 to 0.87), respectively. Conclusion CHI3L1 has a good diagnostic value in patients with chronic liver disease with significant fibrosis and liver cirrhosis. The diagnostic model in combination with other markers like Collagen IV and FIB-4 scores could further improve the diagnostic value and is worthy of further study.

AIM:To investigate the role of p38 MAPK/ATF-2 pathway in C-relative protein ( CRP)-induced endothelial cell activation.METHODS:Human coronary artery endothelial cells ( HCAEC) were cultured and were used between passages 3 and 7.CRP served as a stimulus for endothelial cell activation.Western blotting was performed to de-termine the expression and phosphorylation of eNOS, p38 and ATF2.ELISA was carried out to detect the levels of ICAM-1, VCAM-1 and MCP-1 released from HCAEC.Pharmacological p38 inhibitors SB203580 and SB202190 were used to de-termine the effect of p38/ATF-2 pathway.RESULTS:CRP reduced the p-eNOS level in a concentration-dependent man-ner and induced the release of ICAM-1, VCAM-1 and MCP-1.The p38/ATF-2 pathway was activated by CRP treatment. SB203580 and SB202190 partially rescued p-eNOS level and suppressed the secretion of ICAM-1, VCAM-1 and MCP-1. CONCLUSION:p38MAPK/ATF-2 pathway participates in CRP-induced endothelial activation.

[ ABSTRACT] AIM:To investigate the effects of microRNA-378*( miR-378*) on the survival and apoptosis of human mesenchymal stem cells ( hMSCs ) .METHODS: The expression of miR-378* was determined by microRNA arrays and quantitative real-time PCR ( qRT-PCR) .H2 O2 was used to induce hMSCs apoptosis.By transfection of miR-378*mimic or inhibitor, we up-regulated or down-regulated miR-378* expression in hMSCs.The effect of miR-378*and connective tissue growth factor ( CTGF) on hMSC survival and apoptosis were detected by MTT, LDH, caspase-3/7 and TUNEL assays.RESULTS:The expression of miR-378*was up-regulated in the old hMSCs compared with the young hMSCs.H2 O2 increased the expression of miR-378*, decreased the expression of CTGF.Up-regulation of miR-378*re-sulted in increasing apoptosis and decreasing survival of hMSCs.Conversely, down-regulation of miR-378*resulted in de-creasing cell apoptosis and increasing survival.The regulation of miR-378*on hMSC apoptosis and survival was attenuated by inhibiting the expression of miR-378* and CTGF together.Direct repression of CTGF expression inhibited the hMSC survival and increased apoptosis.CONCLUSION:miR-378*enhances apoptosis of hMSCs by repressing the expression of CTGF.

Objective To quantitatively evaluate the image quality, stability and volume precision in kilovoltage cone beam CT (CBCT) on Varian linear accelerator. Methods The Catphan (R) 600 phantom was repeatedly scanned in the full-fan and half-fan CBCT scanning modes. A simulation fan-beam CT (FBCT) was used as a benchmark and results related to the low contrast resolution, spatial resolution,uniformity and image noise were compared with the CBCT using the treatment planning system. The comparison of image quality and long-term stability and volume precision was analyzed. Results Spatial resolution was no differences observed between FBCT and CBCT ( 6 lp/cm: 6 lp/cm , T = 18. 00 , P＞ 0. 05 ) .Low contrast resolution was, on average, 1. 65％ and 1. 74％ for both CBCTFull-Fan and CBCTHalf-Fan , and 1. 03％ for the FBCT ( T =6. 00, P ＜ 0. 05). Uniformity was, on average, 0. 005 and 0. 033 for both, and 0. 003 for the FBCT ( T=6. 00 , P ＜0. 05). In terms of image noise, the FBCT images were superior to the CBCT (T=30. 00, P＜O. 05). In valid scan range of the CBCT, reconstructed precision was high. There was no significant time trend in the image quality. Conclusions The image quality of kilovoltage CBCT is inferior to the conventional CT. However, tumor and soft tissues are visible in the CBCT images. The image stability and reconstructed precision is satisfying.

Objective To summary the clinical data of pediatric renal transplantation from multiple renal transplant centers in China,and analyze the factors influencing the therapeutic outcomes of pediatric renal transplantation.Methods From March 1986 to May 2010,the clinical data of 138 children who underwent renal transplantation in eight centers of renal transplantation in China were retrospectively analyzed.Results The one-year patient and graft survival rate was 99.3％ and 95.7％respectively.Acute rejection episodes occurred in 38 cases (27.5％),15 cases suffered delayed graft function (DGF),and graft functions were returned to normal in all recipients within one month.Moreover,other complications included transplant renal artery stenosis in 8 cases (5.8％),ureteral necrosis in 2 cases (1.4％),urinary fistula in 5 cases (3.6％),hypertension in 57 cases (41.3 ％),hyperlipidemia in 38 cases (27.5％),hirsutism in 32 cases (23.2％),drug-induced liver damage in 26 cases (18.8％),urinary tract infection in 25 cases (18.1％ ),gingival hyperplasia in 22 cases (15.9％),pulmonary infection in 21 cases (15.2％),bone marrow suppression in 12 patients (8.7％),herpes simplex in 10 cases (7.2％),and diabetes in 8 cases (5.8％).The body weight was increased by 4 to 13 kg and the body height was increased by 2 to 7 cm during the first year posttransplantation. Conclusion The careful perioperative management, rational use of immunosuppressive agents,strengthening the follow-up management of children and social support,and improving compliance were the key points to obtain good outcomes in pediatric renal transplantation.

Objective To investigate the dose calculation accuracy and feasibility of using kilovoltage cone-beam CT (KVCBCT) for esophageal cancer radiotherapy.Methods Hounsfield unit (HU) values and profile along the horizontal line of Catphan (R) 600 phantom in KVCBCT images acquired on Trilogy linear accelerator were compared to those in the planning CT.The KVCBCT value-density calibration curve was established.The intensity modulated radiotherapy plans were created on the planning CT images and copied to KVCBCT images.The dose distribution was recalculated by means of the KVCBCT value-density calibration curve in the treatment planning system.The dosimetric comparisons were performed between the KVCBCT and planning CT plans on the phantom and 10 patients with esophageal cancer.ResultsThe KVCBCT value was stable with a maximum variation of 1.6％,and there was no significant time trend.CT value profiles showed good agreement within 1％ variation except the peripheral regions.The dosimetric differences were less than 1.33％and 3.65％for the phantom case and the patient ones,respectively.The dose distribution comparison was also in good agreements.Conclusions The accurate dose caleulation based on KVCBCT for esophageal cancer is feasible.The KVCBCT images can be used for monitoring the dosimetric changes during the treatment.

Objective To compare the difference region of interest volume (ROI) calculation method between Pinnacle and Eclipse treatment planning system. Methods To acquire CT image with 3 of slice thickness (1 mm, 3 mm, and 5 mm). Delineate 1, 2 and 5 slices square and circle contours in Pinnacle treatment planning system. Meanwhile 15 cases that include 5 cases with head neck tumor, 5 with thorax tumor and 5 with abdomen tumor were selected. Those image and ROI were transfer to Eclipse treatment plan system by DICOM RT protocol . The ROI volume was compared between two TPS . Results For ROI with small volume, the volume difference between TPS was obvious (for small volume ROI have 12 times difference, for big volume ROI almost same). The volume difference between TPS was influenced by many factors. The number of ROI slice and the magnitude of ROI was related with the difference between TPS (R2 = 1. 000, P = 0. 000). The CT thickness (R2 = 0. 200, P = 0. 972 ) and the shape of ROI ( R2 =0. 200, P = 0. 089) were not significant factors. The center of ROI on different axis was not affect the volume calculation in Pinnacle, which cause 3% different in Eclipse. The CT thickness was proportional to the ROI volume ( Pinnacle R2 = 0. 548, P = 0. 011; Eclipse R2 = 0. 502, P = 0. 027 ). In clinical case, optic chiasm and Len averagely have more than 35% volume difference between those two TPS. Conclusions We should pay more attention about the difference volume calculation algorithm between Pinnacle and Eclipse,especially when transfer small volume ROI to another TPS, which may have significant difference.

Objective To investigate the advantage of the intensity-modulated radiotherapy treatment (IMRT) by allowing dose heterogeneity in the target volume in esophageal cancer treatment planning.Methods Two sets of 5-field IMRT planning were designed for 10 esophageal cancer patients upon the condition of appropriate clinical tolerance level with the prescription dose of 60 Gy to 95% of the planned target volume (PTV) and the maximum dose of 45 Gy to the spinal cord:the IMRT with rigid restriction of the maximum homogeneous dose to the PTV within 63 Gy prescribing a homogeneous dose ( IMRThom ) and the IMRT allowing dose heterogeneity by loosening the constraints on maximum dose in the PTV to 69 Gy ( IMRTinhom ).Dosimetric comparison was conducted by using dose-volume histograms.Results Compared to IMRThom, the minimum dose (t = -3.37,P =0.012), maximum dose (t = - 23.58,P = 0.000), mean dose ( t = - 4.95, P = 0.002 ), and heterogeneity index ( t = - 11.06, P =0.000) in PTV of the IMRTinhom were all significantly increased, and the values of V5 (t = 6.96, P =0.000), V10(t=5.24,P=0.001) , V15(t=4.73,P=0.002) , V20(t=8.08,P=0.000) , V25(t=8.58,P = 0.000), and mean dose (t = 7.28,P = 0.000) of the normal lungs were all significantly lower.There were no significant differences in all the indexes for the mean dose to the heart and maximum dose to the spinal cord between these 2 set of planning.Conclusions The IMRT plan allowing dose heterogeneity in the PTV escalates the prescription dose and decreases the doses to the lungs.