Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus (SRL) and calcineurin inhibitors (CNI, tacrolimus), on level of Treg in the liver allo-graft recipients, Methods Forty-seven liver transplant recipients with stable liver function were assessed for at least 2 years, and divided into two groups: one composed of 15 patients receiving SRL,and another, of those receiving CNI (32 patients with tacrolimus). Thirty-eight age-matched healthy subjects (HS) were used as normal controls. We examined the expression of CD4, CD25, and Foxp3 in peripheral blood monouclear cells. Treg of every group was analyzed using Cell Quest software.Results SRL significantly increased the prevalence of CD4+ CD25high T cells, compared with HS and CNI group. The prevalence of CD4+ CD25high T cells of CNIs group was significantly lower than that of HS. The percentage of CD4+ CD25high T cells in the total CD4+ T cells was 1.88 % (1.56 %-2. 60 %), 1. 15 % (0. 57 %-l. 48 %) and 0. 84 % (0. 46 %-1. 45 %) in SRL, NS and CNI group,respectively (P<0. 01 or P<0. 05). Foxp3 was expressed in more than 95 % of CD4 + CD25high T cells and less than 20 % of CD4+ CD25low T cells, whereas not expressed in CD4+ CD25- T cells.Conclusion Different immunosuppressive therapy (SRL or CNI) might have different roles in tolerance induction in liver transplant recipients. Namely, SRL promoted the induction of allo-antigen tolerance, but CNI hampered the progression.

A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.

Ferulic acid, an useful compound of Chinese traditional medicine, was used as leading compound. Six ferulic acid derivatives were designed and synthesized based on bioisosterism. Their structures were characterized by IR, 1H NMR, 13C NMR and mass spectra. In vivo experiment showed that ferulic acid derivatives had good inhibitory effects on adenosine diphosphate (ADP) induced platelet aggregation, which were significantly higher than that of Ozagrel.

Objective To explore the effect of hypoxia inducible factor-1α silencing by siRNA on proliferation, apoptosis and necrosis of human renal proximal epithelial cell ( HK-2 )under hypoxia. Methods CoCl2 was used to mimic hypoxia, and siRNA technique was used to silence HIF-1α. HK-2 cells were divided into five groups, including normal culture group,hypoxia culture group, transfection reagent group, negative control group and HIF-1α siRNA group.MTT assay was used to detect the growth inhibition ratio of cells. TUNEL and caspase-3 quantity was used to detect apoptosis. LDH activity in supernatant was detected to evaluate cell necrosis.Real-time PCR and Western blotting were used to detect mRNA and protein of HIF-1α, HIF-2α,glucose transporter 1(Glut-1) and vascular endothelial growth factor (VEGF). Results (1) The transfection efficiency of siRNA was 95%-100%. Under normoxia, the efficiency of siRNA silencing HIF-1α gene reached to 70%, while under hypoxia, it was 97%. (2) The growth inhibition ratio of cells in HIF-1α siRNA group was significantly higher than that of other groups including hypoxia culture group, transfection reagent group and negative control group (all P＜0.05). No significant difference was found in apoptotic ratio of the other four groups except normal culture group (P＞0.05). The LDH level in HIF-1α siRNA group was significantly higher than that of hypoxia culture group, transfection reagent group and negative control group (P＜0.05). (3) The expression of HIF1α, Glut-1, VEGF mRNA and protein in HIF-1α siRNA group was significantly lower than that of hypoxia culture group, transfection reagent group and negative control group (P＜0.05). No significant difference was observed on the level of HIF-2α mRNA and protein in the other four groups except normal culture group (P＞0.05). Conclusion HIF-1α gene silencing can inhibit the mRNA and protein expression of Glut-1 and VEGF, and can aggravate growth inhibition and necrosis of HK-2 cells under hypoxia.

Gallstone ileus is a rare mechanical ileus,which was caused by discharge of giant gall bladder stone to the intestine.Understanding the causes of ileus is the key factor for treatment,and surgical treatment is the treatment of choice.An old patient with gallstone ileus was admitted to the Second Affiliated Hospital of Soochow University in April 2013.Preoperative X ray detection and computed tomography showed gallbladder wall thickening,formation of a sinus tract between the gall bladder and the duodenum,and intestinal ileus in the left iliac region (the diameter of the stone was about 4 cm).The patient received medical treatment for 3 days and then exploratory laparotomy + lithotomy.Gall bladder stones were not detected during the operation,so the gall bladder was preserved.The patient was followed up till December 2013,the sinus tract was disappeared under B sonography,and the cholecystitis was cured.

Objective To investigate the efficacy of transarterial chemoembolization (TACE) combined with autologous DC-CIK cells in treating hepatocellular carcinoma(HCC) of BCLC C-stage. Methods A total of 60 cases with HCC in BCLC C-stage were randomly and equally divided into the study group (n=30) and the control group (n=30). TACE combined with autologous DC-CIK cells was employed in the patients of the study group, while only TACE was adopted in the patients of the control group. The immune function, six-month and one-year survival rates were determined, and the results were compared between the two groups. Results In the study group, the blood T lymphocyte subsets of CD3+CD8+ were significantly increased, while CD3+CD4+ were obviously decreased. When compared with the pretreatment levels, the differences were statistically significant (P<0.05). The six-month survival rate of the study group and the control group was 67.9% and 48.1% respectively (P<0.05), and the one-year survival rate of the study group and the control group was 53.6%and 29.6%respectively (P<0.05). Conclusion For the treatment of HCC in BCLC C-stage, the therapeutic effect of TACE combined with autologous DC-CIK cells is much better than that of pure TACE. Therefore, this therapy is an effective treatment for HCC in BCLC C-stage.

Objective:To evaluate incision scars of transaxillary breast augmentation by different methods of scar assessment.Methods:A retrospective study was carried out on 30 patients (age range 20 to 50 years, with mean age of 32 years) who underwent endoscopic assisted transaxillary type Ⅰ dual plane breast implant augmentation by a same surgeon from August 2014 to November 2016. Scars were estimated by 3 methods which included Vancouver Scar Scale (VSS), Visual Assessment Scale (VAS) and patients' questionnaire.Results:VAS score for left side scars ranged from 0 to 8 and the median was 1. VAS score for right side scars ranged from 0 to 8.3 and the median was 1. A total of 48 scars were scored in the 0-2 point range, representing 80% of the 60 total. VSS score for left side scars ranged from 0 to 11.6 and the median was 0.8. VSS score for right side scars ranged from 0 to 11.3 and the median was 1.2. A total of 46 scars were scored in the 0-2 point range, representing 76.7% of the total 60 breats. The scores between VSS and VAS had significant statistical differences ( P<0.001). 80.0% of our patients regarded scars as unconspicuous or basically invisible in our questionnaire. Conclusions:The majority of transaxillary incision scars recover in favorable status with high patients satisfactory rate. VAS is a practical tool for evaluating transaxillary incision scars. The VSS score is not equivalent to the VAS score when grading scars only by photos.

Objective:To explore the potential serum biomarkers of patients with lupus nephritis(LN)by using two-dimensional electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF/TOF MS),so as to lay the foundation for illuminating pathogenesis.Methods:A total of 40 LN patients were divided into two groups,the active LN group and the inactive LN group,with 20 in each.In addition,20 IgA nephritis patients and 20 healthy volunteers were enrolled as IgAN group and healthy control group.Two-dimensional gel electrophoresis was used to separate and analyze the serum proteins,and MALDI-TOF/TOF MS was applied to the identification of the differentially expressed pro-teins.Results:A total of fifty differentially expressed proteins were identified.Compared with that in healthy control group,23 differentially expressed proteins were discovered in active LN group and inactive LN group,among which,8 proteins were up-regulated and 1 5 proteins were down-regulated.And 1 8 differentially expressed proteins,compared with IgA nephritis group, were found in active LN group and inactive LN group,including 13 up-regulated proteins and 5 down-regulated proteins.Fur-thermore,the number of up-regulated and down-regulated proteins in active LN group,compared with those in inactive LN group,were 4 and 5,respectively.Among the 50 identified differentially expressed proteins,the expression of serum amyloid protein A(SAA )in active LN group was higher than that in the other groups while the expression of complement component C4A in active LN group was lower than that in the other groups.And the expression of chain B (solution structure of double super helix model)in the inactive LN group was higher than that in the other groups.Compared with that in healthy control group,the expression of vitamin D-binding protein isoform 1 precursor,chain A(crystal structure of uncomplexed vitamin D-binding protein)and chain B (a covalent dimer of transthyretin that affects the amyloid pathway)was up-regulated in both ac-tive LN group and inactive LN group,while the expression of the vitronectin precursor,ficolin-2 isoform a precursor and chain A (crystal structure of the catalytic domain of human complement C1 s protease)was down-regulated.Compared with that in IgA nephritis group,the expression of lipoprotein CIII and vitronectin precursor was up-regulated in both active LN group and inactive LN group.Conclusions:Combination of two-dimensional gel electrophoresis and MALDI-TOF/TOF MS is effective for screening and identification of differentially expressed proteins in serum from LN patients.These differentially expressed pro-teins could be used as biomarkers for noninvasive diagnosis and evaluation of LN.Further study on these proteins would be conducive to understanding the pathogenesis of LN.

BACKGROUND:Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication,while repairing skeletal muscles and promoting skeletal muscle regeneration,which is expected to be a novel treatment modality for sarcopenic obesity. OBJECTIVE:To review the biogenesis of extracellular vesicles,their biological functions,their relationship with sarcopenic obesity,and recent advances in the pathogenesis,diagnosis,and treatment of sarcopenic obesity. METHODS:The first author performed a computer search of PubMed,Embase,CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity.The search keywords were"extracellular vesicle,exosome,sarcopenic obesity,obese sarcopenia,skeletal muscle regeneration,skeletal muscle mass regulation"in English and Chinese,respectively.The search period was from June 2022 to November 2022.After screening,87 articles were included for further review. RESULTS AND CONCLUSION:Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine,paracrine and endocrine ways.Sarcopenic obesity is a complex multi-factor disease.Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells.Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis,which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity.Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers,but also are a valuable diagnostic indicator of sarcopenic obesity.Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration.Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.