[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[Efficacy and prognosis of infant kidney transplantation].

Objective: To analyze the effect and prognosis of infant kidney transplantation. Methods: Clinical data of 37 cases of infant kidney transplantation under 3 years old in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from June 1, 2017 to July 31, 2022 were retrospectively collected. These 37 cases included 31 primary kidney transplantation and 6 secondary kidney transplantation. Kaplan-Meier method was used to draw the survival curve of the transplanted kidney and the recipient, and the prognosis and complications were analyzed. Median follow-up was 18 months (range: 6-66 months). Results: The recipients were 20 males and 17 females, with a median age of 16 months (range: 2 months, 26 days to 36 months) and a median weight of 8 kg (range: 3.2 to 14.0 kg). The youngest child was only 2 months, 26 days old, and weighed only 3.2 kg. The most common primary disease of recipients was congenital nephrotic syndrome (13 cases, 41.9%). Intra-abdominal transplantation occurred in 19 cases (51.3%) and intra-iliac fossa transplantation occurred in the remaining 18 cases (48.6%). Postoperative renal function recovery was delayed in 7 cases (18.9%), and thrombosis caused renal function loss in 5 cases (13.5%), of which 4 cases received second renal transplantation and were successful. During the follow-up period, there were 11 cases of acute rejection (29.7%) and 6 cases of CMV pneumonia (16.2%). The estimated glomerular filtration rate 1 year after transplantation was higher than that 1 month after surgery [(101.9±22.1) vs (71.1±25.6) ml/(min·1.73m2), P<0.001], and remained constant 2 years after transplantation. Both the 1-year and 2-year survival rates of the transplanted kidney were 85.3%, and both the 1-year and 2-year survival rates of the recipients were 96.8%. Conclusion: Although the implementation of infant kidney transplantation is difficult, it can still achieve relatively satisfactory efficacy and prognosis.

[Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma].

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

[Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model].

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

[Technical summary and experiences of urinary reconstruction in mouse kidney transplantation].

The present paper summarizes the methods and technical key points for urinary reconstruction in mouse kidney transplantation. Both bladder patch and ureter implantation techniques are feasible options for urinary reconstruction in mouse kidney transplantation. The dominant complication in bladder patch technique is ischemic necrosis of patch and distal ureter and is associated with donor mouse strains and surgical skills. The most common complication in ureter implantation technique is urine leakage and is related to recipient mouse gender and technical skills. The key technical points for bladder patch method are estimation of blood supply for bladder patch and properly trimming and suturing bladder walls. The key points for ureter implantation method are properly trimming and fixation of the ureter. Comparing with the bladder patch, the ureter implantation technique is faster, its complications are easier to be repaired by secondary surgery, but the risk of urine retention is higher at late time. The timeliness of surgical intervention is a key factor for successfully repairing the early urinary complications.

[Study on heme oxygenase-1 and HAP model for the diagnosis of chronic hepatitis B-related liver fibrosis].

Objective: To determine the diagnostic value of plasma heme oxygenase 1 (HO-1) in the occurrence, development, and pathological stages of chronic hepatitis B-related liver fibrosis. Methods: 211 outpatients and inpatients with chronic hepatitis B (CHB) and 57 healthy controls who visited the Third Hospital of Hebei Medical University were selected. Simultaneously, clinical data, peripheral blood routine and serum biochemical test results of the research subjects were collected. Plasma HO-1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Liver fibrosis (S1 ~ 4) was staged according to liver biopsy and liver stiffness measurement (LSM). Statistical analysis: binary logistic regression was used to analyze the independent risk factors of hepatitis B-related liver fibrosis to establish a diagnostic model, and the receiver operating characteristic curve (ROC) was used to compare and analyze the staging efficiency of HO-1, new model, FIB-4 and APRI for the diagnosis of liver fibrosis. Results: Plasma HO-1 levels were significantly higher in CHB patients than healthy controls [10.11 (7.08 ~ 13.12) ng/ml and 6.71 (5.56 ~ 8.45) ng/ml, (P < 0.001)]. There were 37, 38, 38, and 98 cases with liver fibrosis stages S1, S2, S3, and S4, respectively and plasma HO-1 level was (6.91 ± 2.80) ng/ml, (8.24 ± 2.44) ng/ml, (9.96 ± 3.46) ng/ml, (12.65 ± 3.70) ng/ml, P < 0.001. HO-1, albumin, and platelets (PLT) were independent risk factors for liver fibrosis. A HAP model was established. HAP, FIB-4 and APRI sensitivity and specificity for the diagnosis of liver fibrosis staging were as follows: ≥S2 were 84.62%, 72.35 %, 81.18% and 83.78%, 81.08%, 67.57%; ≥S3 were 80.15%, 82.09%, 85.82% and 88.64%, 76.19%, 60.32%; S4 were 90.82%, 82.29%, 86.46% and 74.37%, 65.77%, 48.65%, respectively. Conclusion: Plasma HO-1 level can reflect the severity of liver fibrosis. HAP diagnostic model can more accurately mirror the process of liver fibrosis than FIB-4 and APRI, and point clinical diagnosis and prognosis assessment.

[Predictive value of platelet aggregation rate in hemodynamically significant patent ductus arteriosus in preterm infants].

Objective: To explore the predictive value of platelet aggregation rate in patent ductus arteriosus in preterm infants. Methods: This prospective nested case-control study enrolled 72 preterm infants with gestational age<32 weeks, who were admitted to Neonatal Intensive Care Unit of Xuzhou Central Hospital from August 2017 to October 2019. The echocardiography was performed on the 4th to 5th day after birth, and the preterm infants who met the diagnostic criteria of hemodynamically significant patent ductus arteriosus (hsPDA) were included into hsPDA group, and the control group was comprised of matched preterm infants with non-hsPDA according to the proportion of 1∶2. The basic characteristics of the preterm infants were recorded, and their complete blood counts and platelet aggregation function were examined. Clinical data were compared by student's t test and chi-square test between the two groups. The risk factors and their predictive values were analyzed by binary logistic regression analysis and receiver operating characteristic curve. Results: There were 24 preterm infants (16 boys) in the hsPDA group, and 48 (30 boys) in the control group. The incidence of neonatal respiratory distress syndrome (NRDS) grade II-IV in the hsPDA group was higher than that in the control group (67% (16/24) vs. 27% (13/48), χ²=10.422, P=0.001). The thrombocytocrit and adenosine diphosphate-induced platelet aggregation rate in the hsPDA group were lower than those in the control group (0.002 1±0.000 9 vs. 0.002 8±0.000 9, 0.21±0.10 vs. 0.32±0.07, t=-3.043 and -5.093, P=0.004 and <0.01, respectively); while the platelet volume in the hsPDA group was greater than that in the control group ((10.3±2.4) vs. (9.2±2.0) fl, t = 2.713, P = 0.033). The other platelet parameters (platelet count, platelet distribution width, and large platelet ratio) and platelet aggregation rate induced by other inducers (collagen, epinephrine and arachidonic acid) were not significantly different between the two groups (all P>0.05). The low platelet aggregation rate induced by adenosine diphosphate and low thrombocytocrit were independent risk factors for hsPDA in preterm infants (OR=4.525 and 3.994, 95%CI: 1.305-15.689 and 1.143-13.958, respectively). And the adenosine diphosphate-induced platelet aggregation rate had moderate predictive value for hsPDA in preterm infants, as the area under the receiver operating characteristic curve was 0.809, and the cutoff value was 0.245 with 0.67 sensitivity and 0.86 specificity. Conclusions: Poor platelet aggregation function and low thrombocytocrit are independent risk factors for hsPDA in preterm infants with gestational age<32 weeks. Low platelet aggregation rate induced by adenosine diphosphate has moderate predictive value for hsPDA patency.

Characterization of a hospital-based gastroenteritis outbreak caused by GII.6 norovirus in Jinshan, China.

An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.

[Association between congenital heart disease and medication taken during pregnancy among women of childbearing age].

Objective: To analyze the relationship between medication taken during pregnancy and congenital heart disease of the newborns. Methods: A large cross-sectional survey was conducted between August and November 2013. A questionnaire survey was conducted among the childbearing aged women, selected through multistage stratified random sampling in Shaanxi from 2010 to 2013. All of the childbearing aged women under study were in pregnancy and with definite pregnancy outcomes. Multivariable Poisson regression was conducted for data analyses. Results: A total of 28 680 cases were included in this study. The proportion of medication taken at any time during pregnancy was 16.0%, and the prevalence of congenital heart disease among the newborns was 67.9/10 000. After adjustment for factors as general demographic characteristic, history of heart disease and drug allergy and the situation of disease during pregnancy of these women, results from the multivariable Poisson regression showed that, factors as taking drugs (RR=1.95, 95%CI: 1.42- 2.68), cold medicine (RR=1.68, 95%CI: 1.07-2.64), antibiotics (RR=1.90, 95%CI: 1.25-2.90), salicylates (RR=5.01, 95%CI: 1.84-13.64) and antifungal drugs (RR=10.22, 95%CI: 3.25-32.19) during pregnancy were all related to congenital heart disease, and with the history of taking cold medicine (RR=1.90, 95%CI: 1.01-3.61), antibiotics (RR=2.18, 95%CI: 1.17-4.06), salicylates (RR=6.07, 95%CI: 1.45-25.41), antifungal drugs (RR=21.01, 95%CI: 4.17-105.87) and other drugs (RR=2.31, 95%CI: 1.19-4.47) during early pregnancy. These factors were with higher risks for congenital heart disease. Conclusion: Women of childbearing age who took cold medicine, antibiotics, salicylic acid drugs, antifungal drugs and other drugs during early pregnancy would increase the risks related to congenital heart diseases.

[A propensity score-matched study on relationship between maternal respiratory infection in early pregnancy and gestational age].

Objective: To explore the association between maternal respiratory infection in early pregnancy and gestational age of single live birth. Methods: A face to face questionnaire survey was conducted among child bearing aged women in 30 counties (district) of Shaanxi province selected through stratified multistage sampling. Propensity score (PS) matched (1∶1) analysis was used to match participants with respiratory infections to those without respiratory infections. A multilevel linear model was used to investigate the association between respiratory infections and gestational age. Through the control of the confounders step by step, three models were established in this study: model 1 for the variable of respiratory infections before PS matching, model 2 was adjusted for variables in model 1 plus some other individual differences of mother and baby, and model 3 for the variable of respiratory infections after PS matching. Results: Of 28 848 child bearing aged women surveyed, 3 676 (12.74%) had respiratory infections in early pregnancy. After PS matching, 2 762 pairs were matched. Analysis with model 1 indicated that a decrease of 0.111 week (P<0.001) in gestational age was associated with a respiratory infection during the first trimester. Analysis with model 2 and model 3 indicated that a decrease of 0.058 week (P=0.025) and a decrease of 0.076 week (P=0.036) were associated with respiratory infection during the first trimester, respectively. Conclusion: The respiratory infection during the first trimester was associated with the decrease of the gestational age of newborn.

[Association between illness and mental status in pregnant women and birth defects].

Objective: To understand the prevalence of birth defects, related diseases and mental status of women during pregnancy in Shaanxi province and to analyse the major risk factors on birth defects and congenital heart disease. Possible association between maternal diseases or mental status and the risk of birth defects, was also explored. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. The whole survey was from Jury 2013 to November 2013. Logistic regression method was used to analyze the association between maternal diseases, mental status during pregnancy and birth defects. Results: The overall prevalence of birth defects was 195.04 per 10 000 in Shaanxi. Among the 29 121 mothers participating in this study, 51.1% developed illness and 6.8% "changed their mental status during pregnancy. After adjusting all the confounding factors, results showed that, histories of cold" , fever, and intrahepatic cholestasis were (OR=1.33, 95%CI: 1.10-1.61, OR=1.54, 95%CI: 1.09-2.16, and OR=32.77, 95%CI:4.08-263.04) respectively, during pregnancy that related to birth defects. Self-reported unstable mental status (OR=1.60, 95%CI: 1.19-2.15) and family friction (OR=2.07, 95%CI: 1.12-3.79) were both related to the birth rates. Histories of cold and fever (OR=1.59, 95%CI: 1.28-1.98; OR=1.43, 95%CI: 1.48-4.00), during early pregnancy, unstable mental status during mid-pregnant period (OR=1.52, 95%CI: 1.05-2.19), unstable mental status during late-pregnant period (OR=1.63, 95%CI: 1.05-2.19) and family friction during late-pregnant period (OR=2.89, 95%CI: 1.16-7.20) were found to be related to birth defects. Compared with those without history of cold, those with the history of cold during first (OR=1.24, 95%CI: 1.02-1.52) and second stages (OR=2.06, 95%CI: 1.30-3.26) of pregnancy were more likely to bear fetus with birth defects. Compared with those without these histories, those with histories of fever (OR=1.49, 95%CI: 1.04-2.13), emotional problem (OR=1.71, 95%CI: 1.19-2.45) and related diseases (OR=2.67, 95%CI: 1.32-5.39) during the first period of pregnancy were more likely to bear fetus with birth defects. Conclusion: The incidence of birth defects in Shaanxi was high. Histories of cold, fever, unstable mental status and family friction during pregnancy, seemed to have increased the risks of bearing child with birth defects.

[Relationship between air pollution exposure during pregnancy and birth weight of term singleton live-birth newborns].

Objective: This study explored the association between air pollution exposure and birth weight by using the multilevel linear model, after controlling related meteorological factors and individual differences of both mothers and babies. Methods: Women of childbearing age who were pregnant in Xi'an from 2010 to 2013, were selected as objects of this study. Multistage random sampling method was used to select 4 631 subjects followed by a self-designed questionnaire survey. Data related to quality of air and meteorology were gathered from routine monitoring system. Gestational age and date of birth, together with the average levels of air pollution were calculated for each trimester on each mother, and then the impact of air pollution on birth weight was assessed. A multilevel linear model was employed to investigate the association between the levels of exposure to air pollution by birth weight. Confounding factors were under control. We established three models in this study: Model 1 which involving the variable of air pollution exposure. Model 2 was adjusted for variables in Model 1 plus some other individual differences of both mother and baby. Model 3 was adjusted for variables in Model 2 plus meteorological factors. Results: There were significant differences seen in birth weight within the subgroups of gender, gestational age, mother's reproductive age, maternal education, residential areas and family incomes (P<0.01) of the infants. However, there was no difference found in Model 1 (P>0.05). Data from Model 3 indicated that a decrease of 13.3 g(10.9 g in Model 2) and 6.6 g (5.9 g in Model 2) in birth weight that were associated with an increase of 10 µg/m(3) in the average level of NO(2) and PM(10) during the second trimester; A decrease of 13.7 g (9.8 g in Model 2) in birth weight was associated with an increase of 10 µg/m(3) in the average level of NO(2) during the third trimester. Conclusion: After controlling for meteorological factors, the levels of exposure to NO(2) and PM(10) during the second trimester and NO(2) during the third trimester were negatively associated with birth weight.

[Experiences of rescuing infective arterial hemorrhage and pseudoaneurysm in DCD kidney transplantation].

Objective: To summarize experiences of rescuing arterial hemorrhage and pseudoaneurysm caused by infection in donation after cardiac death (DCD) kidney transplantation. Methods: A total of 198 consecutive DCD kidney transplantations between 1 June 2013 and 30 July 2016 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The means of rescuing infective arterial hemorrhage and pseudoaneurysm after operation and their therapeutic effects were summarized. Results: A total of 5 infective arterial hemorrhage, 2 infective pseudoaneurysm with hemorrhage, and 1 infective pseudoaneurysm developed in 198 DCD kidney transplantation recipients with total morbidity of 4.0%, and the morbidity of fungal infection accounted for 2.5%. One case received open surgical therapy. Two cases were treated with endovascular interventional therapy. Five cases received combined treatments of open surgery and endovascular intervention. Selective antibiotics were used based on drug sensitivity test postoperation. The wound was drained, and the drainage was repeatedly cultured to monitor the pathogen till the results turned to negative. Five patients received graft nephrectomy and were restored to hemodialysis. Two patients were successfully rescued with stable graft function. One case died. The mortality of patient was 1/8. Graft loss rate was 5/8. Both patients with stable graft function were mainly treated by intervention. Conclusions: Infective arterial hemorrhage and pseudoaneurysm were primary risk factors causing patient/graft death postoperation in DCD kidney transplantation. Endovascular therapy can be used as an effective rescuing method under the circumstance of infection. The measure allows opportunity of successfully rescuing kidney graft and deserves recommendation.

[Massive hemorrhage caused by fungal infections after donation-after-cardiac-death kidney transplantation: clinical features, prevention and treatment experience].

OBJECTIVE: To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation. METHODS: A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized. RESULTS: Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group. CONCLUSIONS: Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.

[Identification and significance of myeloid-derived suppressor cells in peripheral blood of breast cancer patients].

OBJECTIVE: To investigate the presence, biological features, and clinical significance of myeloid-derived suppressor cells (MDSCs) in breast cancer patients. METHODS: Eighty-four cases of breast cancer, 37 cases of benign breast tumor and 21 cases of healthy individuals were included in this study. Samples of peripheral blood (2 ml) were collected, and in the breast cancer patients, blood samples were taken both before and after treatment. Flow cytometry using anti-CD11b, CD33, CD14 and HLA-DR antibody was conducted to identify the unique membrane markers of MDSCs, and statistical analysis was performed to explore the relationship between MDSCs and clinical factors. Cell isolation and in vitro assay were used to test T cell function. RESULTS: CD11b(+) CD33(+) CD14(-) MDSCs were present in the blood of breast cancer patients, and these MDSCs were histologically of mononuclear cells. Cell proliferation assay confirmed that MDSCs inhibited proliferation of homologous T cells in vitro. MDSCs levels in patients with breast cancer, benign disease and the health control were (15.93±3.17)%, (8.92±4.42)% and (5.02±2.75)%, respectively, with a statistically significant difference (P<0.001) between breast cancer patients and the other subjects (patients with benign lesions and healthy controls). The expression level of MDSCs in patients with breast cancer was associated with surgical treatment, but not with age, disease stage, lymph node metastasis, ER or PR expression. MDSCs levels were significantly lower in post-operative patients[(7.83±3.78) %] than the (15.37±2.49) % in patients before surgery (P<0.001). CONCLUSIONS: The results of this study demonstrate that MDSCs are present in the peripheral blood of breast cancer patients and the level of MDSCs is associated with surgical treatment. Our findings suggest that CD11b(+) CD33(+) CD14(-) MDSCs are likely involved in breast cancer initiation and development, and may become a novel biomarker to facilitate diagnosis and to predict clinical outcomes of breast cancer.

Tumor necrosis factor-like weak inducer of apoptosis regulates the phenotype and cytotoxic activity of goat uterine natural killer cells.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has an important role in the promotion of cell proliferation, migration, and differentiation. However, very little is known about the role of TWEAK in modulating uterine natural killer (uNK) cells' comprehensive functions in ruminants. In the present study, the effects of TWEAK on goat uNK cells were investigated by measuring their cytotoxic function and phenotype as well as cytokine expression in vitro. The results showed that TWEAK protein could be detected in the goat endometrium during estrous cycle and pregnancy. However, a significant increase in ( < 0.05) TWEAK protein levels was observed during very early pregnancy when compared with that during mid pregnancy and later pregnancy as well as during different phases of estrous cycle. Tumor necrosis factor-like weak inducer of apoptosis did not affect proliferation but did decrease ( < 0.05) the cytotoxic activity of uNK cells in vitro. Furthermore, the percentage of CD56/NKp46 uNK cells incubated with TWEAK-containing medium was greater ( < 0.05) compared with those treated with control medium. In addition, uNK cells incubated with TWEAK medium were associated with lesser ( < 0.05) secretion levels and protein expression of interferon-γ (IFN-γ) compared to those incubated with control medium. However, no differences ( > 0.05) could be observed for the secretion levels and protein expression of vascular endothelial growth factor (VEGF) in the uNK cells incubated with TWEAK-containing medium compared with those incubated with control medium. The present preliminary observations indicate that TWEAK has a biological effect on phenotype of uNK cells as well as the secretion and expression of IFN-γ by uNK cells in goats. Moreover, TWEAK decreases the cytotoxicity of goat uNK cells in vitro.