[Analysis of the efficacy and influencing factors of sodium channel blockers in the treatment of focal epilepsy in infants under 6 months of age].

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.

[Curing mode of universal adhesives affects the bond strength of resin cements to dentin].

OBJECTIVE: To determine the effects of curing mode of one-step and two-step universal adhesives on the micro-tensile bond strength (µTBS) of different dual-cure resin cements to dentin. METHODS: One-step universal adhesive Single Bond Universal (SBU), and two-step universal adhesive OptiBond Versa (VSA) were chosen as the subjects, one-step self-etching adhesive OptiBond All in One (AIO) and two-step self-etching adhesive Clearfil SE Bond (SEB) were control groups, and two dual-cure resin cements RelyX Ultimate (RLX) and Nexus 3 Universal (NX3) were used in this study. In this study, 80 extracted human molars were selected and the dentin surface was exposed using diamond saw. The teeth were divided into 16 groups according to the adhesives (AIO, SBU, SEB, VSA), cure modes of adhesives (light cure, non-light cure) and resin cements (RLX, NX3). The adhesives were applied on the dentin surface following the instruction and whether light cured or not, then the resin cements were applied on the adhesives with 1 mm thickness and light cured (650 mW/cm(2) for 20 s. A resin was built up (5 mm) on the cements and light cured layer by layer. After water storage for 24 h, the specimens were cut into resin-cement-dentin strips with a cross sectional area of 1 mm×1 mm and the µTBS was measured. RESULTS: Regarding one-step universal adhesive (SBU) light cured, the µTBS with RLX [(35.45±7.04) MPa] or NX3 [(26.84±10.39) MPa] were higher than SBU non-light cured with RLX [(17.93±8.93) MPa)] or NX3 [(10.07±5.89) MPa, P<0.001]. Compared with AIO, light-cured SBU combined with RLX presented higher µTBS than AIO group [(35.45±7.04) MPa vs. (24.86±8.42) MPa, P<0.05]. When SBU was not lighted, the µTBS was lower than AIO [(17.93±8.93) MPa vs. (22.28±7.57) MPa, P<0.05]. For two-step universal adhesive (VSA) and control adhesive (SEB), curing mode did not affect the µTBS when used with either RLX or NX3 (25.98-32.24 MPa, P>0.05). CONCLUSION: Curing mode of one-step universal adhesive may affect the µTBS between dual-cure resin cements and dentin, while for two-step universal adhesive, the curing mode and the type of resin cements did not influence the µTBS.

Galectin-9 in Combination With EX-527 Prolongs the Survival of Cardiac Allografts in Mice After Cardiac Transplantation.

Galectin-9 (Gal-9), a member of the galectin family, has a variety of biologic activities. However, its role in allografts is not fully clarified yet. The relationship between interleukin-17 (IL-17) and Gal-9 and the role of Gal-9 in T(H)17-cell differentiation also remain unclear. We built a murine cardiac transplantation model, which we treated with Gal-9 and/or EX-527, a specific Sirtuin-1 inhibitor. Afterwards, flow-cytometric analysis and reverse-transcription polymerase chain reaction were used to detect the number of T(H)17 cells and the expression of key factors involved in the differentiation of T(H)17 cells; in addition, the survival times of cardiac transplanted mice in different groups were recorded. The levels of circulating T(H)17 cells were found to increase in the peripheral blood of mice that exhibited acute rejection (AR) after heart transplantation, which was determined to be correlated with the rejection grade. Gal-9 or EX-527 can inhibit the activation and differentiation of T(H)17 cells and effectively suppress T(H)17-cell-mediated AR. These data provide new evidence for the potential regulatory effects of Gal-9 in alloimmune responses in a murine model of heart transplantation, and suggest the combined use of galectin-9 and EX-527 may be a powerful method to induce tolerance of fully mismatched murine cardiac allografts.

Ambrisentan improves the outcome of rats with liver transplantation partially through reducing nephrotoxicity.

OBJECTIVE: Tacrolimus is a potent immunosuppressive agent mainly used for allogeneic solid organ transplantation. Although usage of tacrolimus led to a significant increase in short-term allograft survival, the long-term morbidity remains high. Endothelin-1 (ET-1) is reported to be associated with increased vascular resistance, CNI-induced nephrotoxicity and chronic rejection. MATERIALS AND METHODS: In the present study, we first detected the serum and renal ET-1 level of rats treated by tacrolimus and found strong positive correlations were existed between the ET-1 level and the tacrolimus dosage and treated time. Furthermore, we studied the protective effect of ambrisentan in liver transplantation rats when co-administrated with tacrolimus. Healthy inbred male Wistar and Sprague-Dawley (SD) rats were used in this study. The post-operative general condition, transplantation survival time, hepatic aminotransferase, serum IFN-γ and level kidney injury biochemical index were recorded and compared to evaluate the immune response and outcomes in the recipient rats after liver transplantation. RESULTS: Our results indicate that ambrisentan prevents the changes of ET-1 content in rats of non-operative treatment group and reduced the nephrotoxicity in the rats with liver transplantation. Rats from ambrisentan co-administration group exhibited good postoperative condition and prolonged survival. CONCLUSIONS: Ambrisentan reverted some effects induced by tacrolimus in the kidney and indicated a positive potential for therapeutic benefit.

Effects and mechanisms of tacrolimus on development of murine Th17 cells.

Tacrolimus (Tac, FK506) is a widely used T-cell-targeted immunosuppression drug known as a calcineurin inhibitor. However, its pharmacologic effects on T-helper type 17 (Th17) cells have not been fully elucidated. Herein, we demonstrate that Tac inhibits Th17 cell differentiation and proliferation, and expression of IL-17 messenger RNA. The proposed mechanism is that Tac inhibits calcineurin and T-cell receptor stimulation-induced cell division. Because Th17 cells participate in allograft rejection, the results of the present study suggest a novel model of immunosuppression effects of Tac. In addition, they provide further implications for the therapeutic immunosuppression effects of Tac on allograft rejection.

Liver transplantation for hepatitis B virus-related hepatocellular carcinoma: one center's experience in China.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer worldwide, with more than half a million identified cases and about a similar number of subjects succumb to it each year. This study sought to evaluate our results of liver transplantation for HCC to identify prognostic factors. METHODS: Between December 2001 and December 2006, 224 patients (205 men, 19 women; age range, 15-75 years) with HCC underwent orthotopic liver transplantation (OLT) at our center. All grafts were from deceased donors. There were 68 cases within Milan criteria (30.3%), 32 cases beyond Milan criteria but within UCSF (University of California, San Francisco) criteria (14.3%), and 124 cases beyond UCSF criteria (55.4%). RESULTS: The overall 1-, 3-, and 5-year patient cumulative survival rates were 82.5%, 60.1%, and 51.5%, respectively. The survival rates were comparable between patients within Milan and UCSF criteria, but were significantly greater than that of patients beyond UCSF criteria. Multivariate analysis revealed alpha fetoprotein (AFP) >or= 800 microg/L, vascular invasion, and poor tumor differentiation to be independent prognostic factors. CONCLUSION: OLT is a safe and effective treatment for hepatitis B virus-related HCC. Compared with Milan criteria, UCSF criteria successfully expanded the indication without deteriorating the prognosis significantly, while preoperative AFP >or= 800 microg/L, vascular invasion, and poor tumor differentiation indicated poor survival.

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation.

OBJECTIVE: We discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to prevent hepatitis B virus reinfection. Lamivudine was administered to two cases and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical examinations were performed. RESULTS: One of two cases given lamivudine developed reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA was positive in one of the two cases. Three cases given adefovir developed no reinfection with HBV. CONCLUSION: Orthotopic liver transplantation is an effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG prevent hepatitis B virus reinfection.

Cancer in the gastric remnant in China--a review of 33 cases in China.

A review of 33 cases of cancer in the gastric remnant (CGR) including 6 cases in Xian is presented. The detection rate of CGR consisting of different interval groups was 3.16%. The average age was 52.4 years, and Male: female ratio was 10:1. The average interval from the previous operation to the detection was 13.9 years. The interval of the subgroup over 30 years of age at the first operation was shorter than that of the subgroup below 30 years. The highest incidence was found in anastomotic stoma (58.1%) and cardia (32.3%). Borrmann I was the most common pathological type. Confirmed diagnostic rate with fibergastroscope was 81.8%. It is imperative that physician should follow up the patients with stomach remnant. No matter what the results of gastrointestinal barium study may be, the patients should undergo fibergastroscopic examination. The pathogenesis of CGR is also discussed.