The difference of auxiliary examination parameters between margin recurrence and granuloma on enhanced computed tomography after sublobar resection.

Background: Imaging examinations following sublobar resection of lung cancer often find thickened neoplasms around the resection margin. Identifying whether the neoplasms are postoperative recurrence or margin granulomas is vitally important. However, the identification mainly depends on the empirical judgment of the imaging department or clinicians in each clinical center at present, and there are few relevant studies, so it is hard to formulate a relatively unified standard. Therefore, we collected data from patients with thickened neoplasms around the resection margin after sublobar resection and sought to discover how to differentiate granulomas from tumor recurrence. Methods: We examined the clinical records of 15 patients with neoplasms around the margins which identified as malignant in auxiliary examination reports, and received second surgery after first sublobar resection. We collected their postoperative pathology and auxiliary examination parameters. The univariate predictors helpful in distinguishing between recurrence and granuloma were analyzed as a diagnostic test. Results: Of the 15 patients with neoplasms around the resection margin, six were diagnosed with benign granulomas, and nine were diagnosed with primary lung cancer recurrence. The results revealed that age, gender, specific surgical method, maximum standardized fluorodeoxyglucose uptake value (SUVmax), and follow-up time were not significantly different, but there were significant differences in enhanced computed tomography (CT) values in several analyses, which calculated by the hospital imaging system. The maximum CT values of the tumor recurrence and granuloma were 104.9±8.051 and 130.3±7.017 (P=0.045), the minimum CT values (15.67±5.113 vs. -17.17±4.826, P=0.0007) and in the floating range CT values (148.00±5.471 vs. 88.11±7.671, P<0.0001), respectively. Conclusions: Differentiating between tumor recurrence and granulomas after sublobar resection remains difficult. However, examining the differences in enhanced CT allows the clinician to make an informed diagnosis that aids further investigation and treatment.

Digital single-operator cholangioscopy for biliary stricture after cadaveric liver transplantation.

BACKGROUND: Biliary strictures after liver transplantation (LT) remain clinically arduous and challenging situations, and endoscopic retrograde cholangiopancreatography (ERCP) has been considered as the gold standard for the management of biliary strictures after LT. Nevertheless, in the treatment of biliary strictures after LT with ERCP, many studies show that there is a large variation in diagnostic accuracy and therapeutic success rate. Digital single-operator peroral cholangioscopy (DSOC) is considered a valuable diagnostic modality for indeterminate biliary strictures. AIM: To evaluate DSOC in addition to ERCP for management of biliary strictures after LT. METHODS: Nineteen patients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between March 2019 and March 2020 at Beijing Chaoyang Hospital, Capital Medical University, were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis. Biliary strictures after LT were classified according to the manifestations of choledochoscopic strictures and the manifestations of transplanted hepatobiliary ducts. RESULTS: Twenty-one biliary strictures were found in a total of 19 patients, among which anastomotic strictures were evident in 18 (94.7%) patients, while non-anastomotic strictures in 2 (10.5%), and space-occupying lesions in 1 (5.3%). Stones were found in 11 (57.9%) and loose sutures in 8 (42.1%). A benefit of cholangioscopy was seen in 15 (78.9%) patients. Cholangioscopy was crucial for selective guidewire placement prior to planned intervention in 4 patients. It was instrumental in identifying biliary stone and/or loose sutures in 9 patients in whom ERCP failed. It also provided a direct vision for laser lithotripsy. A space-occupying lesion in the bile duct was diagnosed by cholangioscopy in one patient. Patients with biliary stricture after LT displayed four types: (A) mild inflammatory change (n = 9); (B) acute inflammatory change edema, ulceration, and sloughing (n = 3); (C) chronic inflammatory change; and (D) acute suppurative change. Complications were seen in three patients with post-interventional cholangitis and another three with hyperamylasemia. CONCLUSION: DSOC can provide important diagnostic information, helping plan and perform interventional procedures in LT-related biliary strictures.

Preparation and application of a novel monoclonal antibody specific for human B7-H3.

Human B7-H3 (CD276), as a new member of the B7 family has been demonstrated to mediate T cell proliferation and the production of interferon­Î³. Two isoforms of B7-H3 have been identified in humans, 2IgB7­H3 and 4IgB7­H3. Since the costimulatory functions of the two isoforms remains to be fully elucidated, there are disagreements regarding their expression patterns as well as the T cell responses. In the present study, a single mouse anti­human monoclonal antibody (mAb), specific for 2IgB7­H3 and 4IgB7­H3 was established, termed 11F4. Using this antibody, the expression of B7­H3 was observed extensively in tumor cell lines, with the exception of certain human hematopoietic cell lines. Subsequently, the fusion proteins of the two B7­H3 isoforms were produced to analyze the biological function of 4IgB7­H3 and 2IgB7­H3 using a Cell Counting Kit­8 assay, and the data revealed that the two isoforms exhibited a similar function in promoting T cell proliferation. In addition, the effect of B7­H3 on the T cells was inhibited by the 11F4 mAb. Overall, the novel antibody produced was observed to exhibit an inhibitory effect offering a useful tool in further investigations of the function of B7-H3 isoforms.

Serum levels of thyroid hormones and thyroid stimulating hormone in patients with biliogenic and hyperlipidaemic acute pancreatitis: Difference and value in predicting disease severity.

OBJECTIVES: To compare retrospectively serum levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) between patients with biliogenic acute pancreatitis (BAP) and those with hyperlipidaemic acute pancreatitis (HLAP), in order to assess their value for predicting the severity of acute pancreatitis (AP). METHODS: Patients with AP were divided into BAP and HLAP groups, then further divided into either a mild AP (MAP) group or a moderately severe AP (MSAP) group. Routine blood parameters were measured. Free tri-iodothyronine (FT3), free thyroxine (FT4) and TSH levels were measured. RESULTS: Seventy-six patients with AP were enrolled in the study. FT3 and TSH levels were significantly higher in patients with MAP than in patients with MSAP. FT4 and TSH levels were significantly lower in the HLAP group than in the BAP group. TSH levels in both MAP and MSAP patients were significantly lower in the HLAP group than in the BAP group. TSH was inversely correlated with triglyceride levels in patients with HLAP. FT3 was a risk factor for MSAP in patients with AP and also demonstrated moderate accuracy in predicting AP severity. CONCLUSIONS: THs and TSH decrease with the severity of AP, especially in patients with HLAP. FT3 may be a useful biomarker for the early assessment of the severity of AP.

Coagulopathy and the prognostic potential of D-dimer in hyperlipidemia-induced acute pancreatitis.

BACKGROUND: Coagulopathy and its association with disease severity in hyperlipidemia (HL)- and non-hyperlipidemia (NHL)-induced acute pancreatitis (AP) are not clear. The present study was to evaluate the relationship between coagulation homeostasis and AP. METHODS: This study included 106 AP patients admitted to our hospital between October 2011 and January 2013. Stratified by disease severity, the patients were divided into two groups: a mild AP (MAP) group (n=69); and a moderately severe AP (MSAP) group (n=37). Based on disease etiology, there were 31 HL-induced AP (HLP) cases and 75 NHL-induced AP (NHLP) cases. The HLP and NHLP groups were compared for parameters of coagulation homeostasis, lipid metabolism, and disease severity. Correlations between disease severity and levels of D-dimer and protein C were investigated, and the prognostic potential of D-dimer was evaluated. RESULTS: Compared with MAP patients, MSAP patients showed higher levels of D-dimer and lower levels of protein C. HLP patients had higher protein C levels than NHLP patients. Both D-dimer and protein C levels were significantly associated with the disease severity, not the disease etiology. D-dimer levels correlated positively with low density lipoprotein cholesterol levels and performed well as a sensitive and specific predictor of disease severity in AP patients, especially in HLP patients. CONCLUSIONS: The coagulation homeostasis is different between HLP and NHLP patients, and HL may be a contributing factor for thrombosis and fibrinolysis in HLP. D-dimer may be a robust marker of disease severity in HLP.

Interleukin-7 is decreased and maybe plays a pro-inflammatory function in primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions, including over-proliferation and apoptosis resistance of auto-reactive lymphocytes. This study aimed to determine the effects of interleukin (IL)-7 on the cytokine production and survival of peripheral blood mononuclear cells and bone marrow mononuclear cells from ITP patients. We found that the plasma IL-7 levels in peripheral blood from ITP patients were lower than that of the normal controls, and it had positive correlation with platelet counts. However, the levels of IL-7 did not change in bone marrow serum of ITP patients compared with that of normal controls. The result of further stimulation experiments in vitro showed that IL-7 up-regulated the apoptosis of autologous platelets, promoted the proliferation and secretion of interferon-γ, tumor necrosis factor-α as well as IL-10 of lymphocyte both from peripheral blood and bone marrow. As the role of IL-7 in apoptosis-resistance and stimulation of pro-inflammatory cytokines, we speculated that decreased IL-7 in peripheral blood, maybe, is a consequence of the negative feedback of the pro-inflammatory function in ITP patients.

[Role of Toll-like receptor 2 in primary immune thrombocytopenia].

The aim of this study was to explore the role of Toll-like receptor (TLR) 2 in primary immune thrombocytopenia (ITP) by detecting TLR2 expression in the peripheral blood lymphocytes of patients with ITP and evaluating the role of TLR2 activation on inflammatory cytokine secretion. A total of 39 ITP patients and 21 normal controls were enrolled in this study. The expression of TLR2 was detected by real-time PCR and flow cytometry, and the concentration of IL-6 and TNF-α in culture supernatant of PBMNC treated with pam3CSK4 for 48 hours were detected by ELISA. The results showed that the expression of TLR2 mRNA in active ITP patients (3.561 ± 0.741) was significantly higher than that in normal controls (1.750 ± 0.314) (P < 0.05), but there was no statistically significant difference between remission ITP patients (2.333 ± 0.448) and normal controls (P > 0.05) . Flow cytometry analysis found that the TLR2 was not expressed on T and B cells, but expressed on all monocytes both from ITP patients and normal controls. Further activation experiment showed that TLR2 activation in vitro could induce the expression of IL-6 (1644 ± 634.0 vs 4111 ± 525.2 pg/ml) and TNF-α (75.37 ± 22.31 vs 326.0 ± 109.9 pg/ml) in PBMNC from ITP patients (both P < 0.05), but just could promote IL-6 expression in normal controls (2119 ± 636.9 vs 4671 ± 315.9 pg/ml)(P < 0.05). It is concluded that the expression of TLR2 mRNA is up-regulated in PBMNC of ITP patients, and this increased TLR2 maybe participate in ITP through inducing secretion of inflammatory cytokines.

Value of D-dimer and protein S for diagnosis of portal vein thrombosis in patients with liver cirrhosis.

OBJECTIVE: To investigate the value of D-dimer and protein S plasma concentrations for diagnosis of portal vein thrombosis (PVT) in patients with liver cirrhosis. METHODS: D-dimer and protein S were quantified, PVT was diagnosed by dynamic enhanced computed tomography and liver function was classified using the Child-Pugh system. Receiver operating curve analysis was performed. RESULTS: D-dimer increased, and protein S decreased, with decreasing liver function in the total study population (n = 188). D-dimer concentrations were significantly higher and protein S concentrations were significantly lower in patients with (n = 51) than those without PVT (n = 137). D-dimer had high specificity and negative predictive value (NPV) in Child-Pugh class A or B patients (cut-off values>0.56 mg/l and >1.18 mg/l, respectively). In class C patients>0.77 mg/l D-dimer had high sensitivity and NPV. Protein S had high sensitivity but low specificity in class A or B patients (cut-off values < 17.4 mg/l and <19.2 mg/l, respectively). CONCLUSION: Plasma D-dimer and protein S are potential biomarkers for PVT diagnosis in patients with cirrhosis. PVT can be excluded when D-dimer is low and protein S is elevated.

Decreasing Poly(ADP-Ribose) Polymerase Activity Restores ΔF508 CFTR Trafficking.

Most cystic fibrosis is caused by mutations in CFTR that prevent its trafficking from the ER to the plasma membrane and is associated with exaggerated inflammation, altered metabolism, and diminished responses to oxidative stress. PARP-1 is activated by oxidative stress and causes energy depletion and cell dysfunction. Inhibition of this enzyme protects against excessive inflammation and recent studies have also implicated it in intracellular protein trafficking. We hypothesized that PARP-1 activity is altered in CF and affects trafficking and function of the most common CF mutant ΔF508 CFTR. Indeed, PARP-1 activity was 2.9-fold higher in CF (ΔF508/ΔF508) human bronchial epithelial primary cells than in non-CF cells, and similar results were obtained by comparing CF vs. non-CF bronchial epithelial cell lines (2.5-fold higher in CFBE41o(-) vs. 16HBE14o(-), P < 0.002). A PARP-1 inhibitor (ABT-888, Veliparib) partially restored CFTR channel activity in CFBE41o(-) cells overexpressing ΔF508 CFTR. Similarly, reducing PARP-1 activity by 85% in ileum from transgenic CF mice (Cftr(tm1)Eur) partially rescued ΔF508 CFTR activity to 7% of wild type mouse levels, and similar correction (7.8%) was observed in vivo by measuring salivary secretion. Inhibiting PARP-1 with ABT-888 or siRNA partially restored ΔF508 CFTR trafficking in cell lines, and most ΔF508 CFTR was complex glycosylated when heterologously expressed in PARP-1(-/-) mouse embryonic fibroblasts. Finally, levels of the mature glycoform of CFTR were reduced by peroxynitrite, a strong activator of PARP-1. These results demonstrate that PARP-1 activity is increased in CF, and identify a novel pathway that could be targeted by proteostatic correctors of CFTR trafficking.

[Effects of interferon-γ on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells].

The aim of this study was to investigate the effects of interferon (IFN)-γ on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells (hUC-MSC). hUC-MSC were treated with IFN-γ 10 ng/ml (IFN-γ group) or without IFN-γ (control group). The phenotype of hUC-MSC was detected by flow cytometry. The proliferation status was detected by CCK-8 method, and its differentiation ability was assessed by oil red O and von Kossa staining. The production of PGE-2 was measured by ELISA, and the mRNA expression levels of COX-2, IDO-1 and IDO-2 in hUC-MSC were detected by real-time quantitative PCR. Furthermore, the proliferation of human peripheral blood mononuclear cells (hPBMNC) was evaluated after co-culture with hUC-MSC, IFN-γ pretreatment or not. The results showed that after IFN-γ stimulation, the expression of SSEA-4 on hUC-MSC decreased significantly [(8.15 ± 2.94) vs (16.42 ± 8.5), P < 0.05], and the expression of CD54 increased [(96.64 ± 3.29) vs (84.12 ± 10.73), P = 0.051]. The immunomodulatory property of hUC-MSC on the proliferation of hPBMNC was enhanced (P < 0.05). All the above mentioned effects were IFN-γ concentration-dependent. When hUC-MSC were stimulated by IFN-γ for 24 h, the production of PGE-2 secreted by hUC-MSC decreased significantly (P < 0.01). The mRNA expression level of COX-2 also decreased though the difference did not reach to statistically significant level. Compared with control group, IDO-1 expression level in IFN-γ group increased significantly (P < 0.01), and the mRNA expression level of IDO-2 remained unchanged. It is concluded that IFN-γ can influence the phenotype of hUC-MSC and enhance the immunomodulatory property of hUC-MSC.

Elevated interleukin-27 enhances the polarization of Th1/Tc1 cells and the production of proinflammatory cytokines in primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease with many immune dysfunctions. Interleukin-27 (IL-27) can regulate T cell differentiation. However, it is unclear whether IL-27 correlates with the dysfunctions of T cell differentiation in ITP patients. Thus, to determine the roles of IL-27 in ITP, we studied the expression of IL-27/IL-27 receptor in ITP patients. The results indicated that the levels of IL-27 in the plasma of untreated active ITP patients were higher than in normal controls. We next evaluated the contribution of IL-27 to T cell differentiation. Our results indicated that IL-27 increased T-bet expression, inhibited GATA-3 and ROR-γt expression, and promoted the secretion of tumor necrosis factor-α, interferon-γ, and granzyme B of peripheral blood mononuclear cells from ITP patients. Also, we confirmed that IL-27 induced the differentiation of T helper (Th)-1 and Tc1 cells. In conclusion, IL-27 might play an important role in the pathogenesis of ITP by inducing the polarization of Th1/Tc1 cells and the production of proinflammatory cytokines.

[Role of measuring the expression levels of a proliferation-inducing ligand and its receptors by real-time fluorescence quantitative method in children with lymphoma].

OBJECTIVE: to investigate the role of a real-time fluorescence quantitative polymerase chain reaction (PCR) in measuring the expression levels of a proliferation-inducing ligand and its receptors expression levels in peripheral blood of children with lymphoma. METHODS: real-time fluorescence quantitative PCR was used to detect the expression levels of a proliferation-inducing ligand and its receptors in patients with Hodgkin disease (n = 10) or non-Hodgkin lymphoma (n = 37) and healthy control (n = 40). The correlation between the mRNA levels of a proliferation-inducing ligand and its receptors and differential stage of malignant lymphoma was analyzed. RESULTS: the results of 47 samples showed that the levels of proliferation-inducing ligand, B cell maturation antigen, transmembrane activator and CAML interactor in the peripheral blood of lymphoma in children were significantly higher than those in normal children (1.13 ± 0.09 vs 0.41 ± 0.09, 1.22 ± 0.11 vs 0.43 ± 0.10, 0.89 ± 0.12 vs 0.35 ± 0.08, all P < 0.05). The level of a proliferation-inducing ligand and its receptors had no significant difference between Hodgkin disease and non-Hodgkin lymphoma (P > 0.05). The level of a proliferation-inducing ligand in I-II stage (0.88 ± 0.06, 0.90 ± 0.08) of malignant lymphoma in children was significantly lower than that in III-IV stage (1.21 ± 0.09, 1.23 ± 0.09, P < 0.05) while the level of its receptors between various stages showed no difference (P > 0.05). CONCLUSION: the real-time fluorescence quantitative PCR has a high sensitivity and reproducibility. A proliferation-inducing ligand may play a great role in the development and progression of malignant lymphoma in children through its receptors of B cell maturation antigen, transmembrane activator and CAML interactor. A proliferation-inducing ligand and its receptors can be established as target molecules for early diagnosis and anti-cancer therapy.

Association of angiotensin-converting enzyme gene 2350G>A polymorphism with myocardial infarction in a Chinese population.

Angiotensin-converting enzyme (ACE) gene 2350G>A polymorphism has the most significant effect on plasma ACE concentrations. But the association between this polymorphism and myocardial infarction (MI) is presently unknown. We carried out a case-control study in the Chinese Han population. ACE2350G>A genotypes of 231 patients with MI and 288 healthy controls were detected by PCR-RFLP. Differences in frequencies of ACE genotypes and alleles and their associations with clinical features were assessed. The distribution of the ACE2350G>A genotypes (GG, GA, and AA) was 20.78%, 51.08%, and 28.14% in the MI group and 31.60%, 46.53%, and 21.87% in controls, respectively (P = .0167).The frequency of the A allele in the MI group was significantly higher than that in controls (53.68% vs 45.14%, P = .0062). The A allele carriers (GA + AA genotypes) had approximately 2-fold increased risk of MI when compared with the GG genotype (odds ratio = 1.76; 95% confidence interval = 1.24-3.52). There were no significant differences among the 3 genotypes in plasma levels of lipids, apolipoproteins, high-sensitivity C-reactive protein, and soluble CD40 ligand in either the MI group or the control group (P > .05). No statistical difference was observed between ACE2350G>A polymorphism and severity of the coronary lesions (P > .05). These results suggest that ACE2350G>A polymorphism is associated with acute MI, and A allele carrier is an independent risk factor for acute MI in the Chinese Han population.

[Gene mutation in the areas of PreC/C and BCP of HBV DNA].

OBJECTIVE: To investigate the gene mutation in the areas of pre core/core (Pre C/C) and basic core promotor (BCP) of HBV DNA and its clinical significance. METHODS: The nt 1 735-1 965 segment of HBV DNA was amplified with PCR in 54 cases with chronic hepatitis B and 10 cases with post-hepatitis cirrhosis. Then the PCR product was sequenced. RESULTS: There were 168 site mutations in 48.5% (33/68) cases with hepatitis B. The first ten mutation sites were nt 1 764 (58.8%), 1 762 (48.5%), 1 799 (21.0%), 1 766 (14.7%), 1 896 (13.2%), 1 754 (8.8%), 1 899 (8.8%), 1 768 (7.4%), 1 814 (7.4%) and 1 913 (7.4%). Three rare mutations of nt 1907, 1 922 and 1 923 were also detected. The mutations of nt 1 896, 1 764 and 1 762 were found in 16.7%, 35.2% and 35.2% of chronic hepatitis, and in 30.0%, 60.0% and 60.0% respectively of post-hepatitis cirrhosis cases. There was statistical significance between the two groups (P < 0.01). CONCLUSION: The mutations in the areas of Pre C/C and BCP of HBV DNA might possibly be associated with liver fibrosis. There are many mutation sites in HBV DNA and mutation occurs frequently, therefore gene sequencing is helpful to the design of gene chip and to clinical application.