Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 BA versus the current routine care. SUMMARY BACKGROUND DATA: Whether steroid therapy post-Kasai portoen-terostomy improves the outcomes of BA remains controversial. Clinical evidence from 2 randomized trials in the UK and USA do not support the routine use of steroid in the treatment of BA. METHODS: In this open-label randomized controlled trial, patients with type 3 BA were randomized to routine postoperative treatment with or without 10 to 12 weeks of adjuvant steroid treatment. The primary outcome was the postoperative jaundice clearance rate with native liver at 6 months. The secondary outcomes included postoperative jaundice clearance rate at 3, 12, and 24 months, survival with native liver at 12 and 24 months, and SAEs within 3 months. RESULTS: Overall, 200 participants were randomized and allocated into either steroid or control group (n = 100/group). The proportion of participants that are jaundice free without liver transplantation was significantly higher in the steroid group than in the control group at 6 months (54.1% vs 31.0%, P = 0.0015). The native liver survival rate was higher postoperatively in the steroid group than in the control group at 12 (66.3% vs 50.0%, P = 0.02) and 24 (57.1% vs 40.0%, P = 0.02) months. The survival time with native liver was significantly longer in the steroid group than in the control group (median survival, steroid vs control: not reached vs 1.21 years, P = 0.02). There were no significant differences between the 2 groups in the mean occurrence of SAEs within 3 months (steroid vs control: 0.63 vs 0.45, P = 0.20). CONCLUSIONS: Postoperative adjuvant steroid intervention improved bile drainage and survival with native liver in type 3 BA patients, without increasing early-stage SAEs.

One microRNA has the potential to target whole viral mRNAs in a given human coronavirus.

MicroRNAs (miRNAs) can repress viral replication by targeting viral messenger RNA (mRNA), which makes them potential antiviral agents. The antiviral effects of miRNAs on infectious viruses have been explored extensively; however, recent studies mainly considered the action modes of miRNAs, neglecting another key factor, the molecular biology of viruses, which may be particularly important in the study of miRNA actions against a given virus. In this paper, the action modes of miRNAs and the molecular biology of viruses are jointly considered for the first time and based on the reported roles of miRNAs on viruses and human coronaviruses (HCoVs) molecular biology, the general and specific interaction modes of miRNAs-HCoVs are systematically reviewed. It was found that HCoVs transcriptome is a nested set of subgenomic mRNAs, sharing the same 5' leader, 3' untranslated region (UTR) and open reading frame (ORF). For a given HCoV, one certain miRNA with a target site in the 5' leader or 3' UTR has the potential to target all viral mRNAs, indicating tremendous antiviral effects against HCoVs. However, for the shared ORFs, some parts are untranslatable attributed to the translation pattern of HCoVs mRNA, and it is unknown whether the base pairing between the untranslated ORFs and miRNAs plays a regulatory effect on the local mRNAs where the untranslated ORFs are located; therefore, the regulatory effects of miRNAs with targets within the shared ORFs are complicated and need to be confirmed. Collectively, miRNAs may bepromising antiviral agents against HCoVs due to their intrinsically nested set of mRNAs, and some gaps are waiting to be filled. In this review, insight is provided into the exploration of miRNAs that can interrupt HCoVs infection.

Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants. Accumulating evidence shows that dysregulated metabolism of glucose, lipids and amino acids are observed in premature infants. Animal and cell studies demonstrate that abnormal metabolism of these substrates results in apoptosis, inflammation, reduced migration, abnormal proliferation or senescence in response to hyperoxic exposure, and that rectifying metabolic dysfunction attenuates neonatal hyperoxia-induced alveolar simplification and vascular dysgenesis in the lung. BPD is often associated with several comorbidities, including pulmonary hypertension and neurodevelopmental abnormalities, which significantly increase the morbidity and mortality of this disease. Here, we discuss recent progress on dysregulated metabolism of glucose, lipids and amino acids in premature infants with BPD and in related in vivo and in vitro models. These findings suggest that metabolic dysregulation may serve as a biomarker of BPD and plays important roles in the pathogenesis of this disease. We also highlight that targeting metabolic pathways could be employed in the prevention and treatment of BPD.

Preventive effect of prophylactic intravenous antibiotics against cholangitis in biliary atresia: a randomized controlled trial.

OBJECTIVE: Biliary atresia (BA) is a neonatal liver disease and requires Kasai portoenterostomy. Many patients develop postoperative cholangitis, resulting in a poor prognosis. The preventive strategy of antibiotics is empirical and lacks a standard regimen. We aimed to analyze the effect of different durations of prophylactic intravenous antibiotics against post-Kasai cholangitis. STUDY DESIGN: A single-center, open-labeled, randomized clinical trial was performed from June 2016 to August 2017. One hundred and eighty BA patients were recruited and randomized into a short-term (n = 90) and a long-term (n = 90) treatment group, and prophylactic intravenous antibiotics were used for 7 versus 14 days, respectively. The primary outcome was the overall cholangitis incidence within 6-months post-Kasai portoenterostomy. The secondary outcomes included cholangitis incidence within 1 and 3 months post-Kasai portoenterostomy, the onset and average episodes of cholangitis, jaundice clearance rate, native liver survival rate, and adverse events within 6-months post-Kasai portoenterostomy. RESULTS: The cholangitis incidence within 6-months post-Kasai in the short-term group was similar to the long-term group (62% vs. 70%, p = 0.27) with intention-to-treat and pre-protocol analysis. There was no significant difference in jaundice clearance rate or native liver survival rate between the two groups. However, the percentage of early onset (61% vs. 38%, p = 0.02) and average episodes (2.4 ± 0.2 vs. 1.8 ± 0.1 episodes, p = 0.01) of cholangitis were lower in the long-term group. CONCLUSION: Long-term intravenous antibiotics can be replaced by the short-term regimen in the general protection against post-Kasai cholangitis.

The pentose phosphate pathway mediates hyperoxia-induced lung vascular dysgenesis and alveolar simplification in neonates.

Dysmorphic pulmonary vascular growth and abnormal endothelial cell (EC) proliferation are paradoxically observed in premature infants with bronchopulmonary dysplasia (BPD), despite vascular pruning. The pentose phosphate pathway (PPP), a metabolic pathway parallel to glycolysis, generates NADPH as a reducing equivalent and ribose 5-phosphate for nucleotide synthesis. It is unknown whether hyperoxia, a known mediator of BPD in rodent models, alters glycolysis and the PPP in lung ECs. We hypothesized that hyperoxia increases glycolysis and the PPP, resulting in abnormal EC proliferation and dysmorphic angiogenesis in neonatal mice. To test this hypothesis, lung ECs and newborn mice were exposed to hyperoxia and allowed to recover in air. Hyperoxia increased glycolysis and the PPP. Increased PPP, but not glycolysis, caused hyperoxia-induced abnormal EC proliferation. Blocking the PPP reduced hyperoxia-induced glucose-derived deoxynucleotide synthesis in cultured ECs. In neonatal mice, hyperoxia-induced abnormal EC proliferation, dysmorphic angiogenesis, and alveolar simplification were augmented by nanoparticle-mediated endothelial overexpression of phosphogluconate dehydrogenase, the second enzyme in the PPP. These effects were attenuated by inhibitors of the PPP. Neonatal hyperoxia augments the PPP, causing abnormal lung EC proliferation, dysmorphic vascular development, and alveolar simplification. These observations provide mechanisms and potential metabolic targets to prevent BPD-associated vascular dysgenesis.

Isolation of a Novel Bat Rhabdovirus with Evidence of Human Exposure in China.

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

Human rabies in China: evidence-based suggestions for improved case detection and data gathering.

BACKGROUND: China still suffers heavily from rabies, although reported human cases continue to decrease year over year. There are far fewer laboratory-confirmed human cases than clinically diagnosed cases, which is a big problem that needs to be addressed. In this report, we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years, in order to promote laboratory diagnosis of rabies. METHODS: From 2005 to 2019, a total of 271 samples from 164 suspected rabies cases were collected from local hospitals by the local Centers for Disease Control and Prevention (CDCs) in China. Saliva, cerebrospinal fluid (CSF), serum (blood) and urine were collected for ante-mortem diagnosis, and brain tissue, neck skin tissue and cornea were collected for post-mortem diagnosis. All of the specimens were tested by reverse transcription-polymerase chain reaction (RT-PCR), and brain tissues were also tested using fluorescent antibody test (FAT). The number of positive test results obtained using different fluids or tissues, and at different stages of the disease, were compared using a chi-square test and a more effective sampling program is recommended. RESULTS: As the national reference laboratory for rabies surveillance in China, our laboratory has tested 271 samples from 164 suspected rabies cases collected by local CDCs since 2005. We found that saliva gave the highest number of positive test results (32%), compared with CSF and other fluids. We also found that serum or blood specimens collected in the last 3 days of life can test positive by RT-PCR. CONCLUSIONS: Serum or blood samples collected in the last 3 days of a patient's life can be used to measure viral RNA, which means that serum samples, as well as saliva and CSF, can be used to detect viral RNA for anti-mortem diagnosis of rabies. Because of our findings, we have modified our "National Surveillance Project for Human Rabies", by adding the collection and testing of serum samples from the end of the survival period. This will improve our national surveillance and laboratory diagnosis of human rabies.

Serum MMP-7 in the Diagnosis of Biliary Atresia.

BACKGROUND: The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. METHODS: We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. RESULTS: The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P < .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with γ glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P < .001). CONCLUSIONS: MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.

Intrahepatic cystic lesions in children with biliary atresia after Kasai procedure.

BACKGROUND: Intrahepatic cystic lesion (ICL) is a common complication for biliary atresia post-Kasai portoenterostomy. The purpose of this study was to review the cases in our hospital and assess the correlation between characteristics of ICL and clinical outcomes. METHODS: We retrospectively analyzed 787 cases of biliary atresia from 2012 to 2016. Demographics, clinical details, and postoperative outcomes were reviewed. RESULTS: A total of 76 patients were diagnosed with ICLs using ultrasound post-Kasai procedure, and the incidence was 9.7%. Preoperative characteristics showed no significant differences between ICL (+) and ICL (-) groups. Nearly 70% (53/76) of the patients with ICLs had a history of cholangitis. The 2-year native liver survival rate was 60.4% for those with a history of cholangitis and 87% for those without (P = 0.017). Further analysis showed that the 2-year native liver survival rate was 42.9% for those diagnosed within 3 months post-Kasai procedure, 54.2% for those diagnosed between 3 and 6 months, and 80.0% for those diagnosed beyond 6 months (P = 0.002), while no significance was observed for type (P = 0.094) or site (P = 0.406) of ICL. CONCLUSION: Patients with ICLs had a high incidence of cholangitis. The prognosis was closely related with the history of cholangitis and the onset time of ICLs. LEVEL OF EVIDENCE: Level II.

Endothelial-to-mesenchymal transition: Pathogenesis and therapeutic targets for chronic pulmonary and vascular diseases.

Endothelial-to-mesenchymal transition (EndoMT) is a process of transdifferentiation where endothelial cells gradually adopt the phenotypic characteristics of mesenchymal cells. This phenomenon was first discovered in embryonic heart development. The mechanisms underlying EndoMT are due to the activation of transforming growth factor-ß, bone morphogenetic protein, Wingless/Integrated, or Notch signaling pathways. The EndoMT can be modulated by pathological processes, including inflammation, disturbed shear stress, vascular stiffness, and metabolic dysregulation. Recent studies have shown that EndoMT is implicated in the pathogenesis of chronic lung diseases, including pulmonary hypertension and lung fibrosis. Lung pathology of bronchopulmonary dysplasia can be mimicked in rodents exposed to hyperoxia as neonates. Although hyperoxic exposure reduces an endothelial cell marker platelet and endothelial cell adhesion molecule but increases a mesenchymal cell biomarker α-smooth muscle actin in vitro in human pulmonary endothelial cells, there is no direct evidence showing EndoMT in the development of bronchopulmonary dysplasia. Both pulmonary hypertension and lung fibrosis occur in long-term survivors with bronchopulmonary dysplasia. In this review, we discuss the EndoMT and its modulation by pathological processes. We then focus on the role of EndoMT in the pathogenesis of these chronic lung diseases, and discuss therapeutic approaches targeting the EndoMT using its negative regulators.

Triple A syndrome: two siblings with a novel mutation in the AAAS gene.

OBJECTIVE: Triple A syndrome is a rare autosomal recessive disorder caused by mutations in the AAAS gene on chromosome 12q13. Its main clinical features are alacrima, achalasia, and adrenal insufficiency, with most patients also having neurological symptoms and autonomic dysfunction. The neurologic manifestations are less well-understood, especially in children. Here, we examine two siblings who were found to have a novel mutation in the AAAS gene and who were found to have subtle, but important, neurologic findings. DESIGN: This is a case report of two siblings. RESULTS: We discuss two siblings exhibiting different signs of the disorder including neurologic dysfunction found at varying ages. Genetic analysis revealed that both patients have the same compound heterozygous mutations in the AAAS gene consisting of one novel mutation (c.500 C>A, A167E) and one previously described mutation (c.1331+1G> A/IVS14+1 G>A). A diagnosis of triple A syndrome was reached based on their clinical and genetic findings. CONCLUSIONS: The unique characteristic of these two cases is the novel mutation in the AAAS gene, which is likely pathogenic. In addition, they showcase the genotype-phenotype variability of the disease, as well as the importance of early identification of the neurologic abnormalities, which can result in early intervention and possibly improved outcomes.

Fatty Acid Oxidation Protects against Hyperoxia-induced Endothelial Cell Apoptosis and Lung Injury in Neonatal Mice.

In neonates, hyperoxia or positive pressure ventilation causes continued lung injury characterized by simplified vascularization and alveolarization, which are the hallmarks of bronchopulmonary dysplasia. Although endothelial cells (ECs) have metabolic flexibility to maintain cell function under stress, it is unknown whether hyperoxia causes metabolic dysregulation in ECs, leading to lung injury. We hypothesized that hyperoxia alters EC metabolism, which causes EC dysfunction and lung injury. To test this hypothesis, we exposed lung ECs to hyperoxia (95% O2/5% CO2) followed by air recovery (O2/rec). We found that O2/rec reduced mitochondrial oxidative phosphorylation without affecting mitochondrial DNA copy number or mitochondrial mass and that it specifically decreased fatty acid oxidation (FAO) in ECs. This was associated with increased ceramide synthesis and apoptosis. Genetic deletion of carnitine palmitoyltransferase 1a (Cpt1a), a rate-limiting enzyme for carnitine shuttle, further augmented O2/rec-induced apoptosis. O2/rec-induced ceramide synthesis and apoptosis were attenuated when the FAO was enhanced by l-carnitine. Newborn mice were exposed to hyperoxia (>95% O2) between Postnatal Days 1 and 4 and were administered l-carnitine (150 and 300 mg/kg, i.p.) or etomoxir, a specific Cpt1 inhibitor (30 mg/kg, i.p.), daily between Postnatal Days 10 and 14. Etomoxir aggravated O2/rec-induced apoptosis and simplified alveolarization and vascularization in mouse lungs. Similarly, arrested alveolarization and reduced vessel numbers were further augmented in EC-specific Cpt1a-knockout mice compared with wild-type littermates in response to O2/rec. Treatment with l-carnitine (300 mg/kg) attenuated O2/rec-induced lung injury, including simplified alveolarization and decreased vessel numbers. Altogether, enhancing FAO protects against hyperoxia-induced EC apoptosis and lung injury in neonates.

Establishment of a Chinese street rabies virus library and its application for detecting neutralizing activity.

BACKGROUND: The injection of rabies immune globulin (RIG) is of the utmost importance in the management of category III exposures to rabies-suspect animals. Because of the high cost and limited availability of existing RIG, one possible replacement for RIG is monoclonal antibodies (MAbs) against the rabies virus (RABV). Consequently, it is necessary to determine the neutralizing activity of the MAbs against rabies viruses, especially street rabies virus. However, the method to detect the neutralizing activity of MAbs against street rabies virus remains undefined. METHODS: To establish a method for detecting the neutralizing activity of MAbs against street rabies virus, we constructed a library consisting of 12 strains of street RABV from 11 provinces in China. Using this street RABV library and the Reed-Muench formula, we established a method for detecting the neutralizing titer of the MAbs. The reliability and repeatability of the method were evaluated by repeatedly measuring the neutralizing activity of a MAb and a post vaccination serum. RESULTS: A total of 12 strains of street RABV were chosen for inclusion in the street RABV library, which covered six Chinese lineages (China I-China VI) and grew to high titers in N2A cells (> 105 FFD50/ml). On the basis of the library, we constructed the method to detect the neutralizing activity of the MAbs. The results of repeatedly measuring the MAbs and positive serum showed excellent reliability and repeatability of the method established in this study. CONCLUSIONS: This study established a street RABV library reflecting the epidemiological features of Chinese rabies viruses, which provides a platform for detecting the neutralizing activity of MAbs against rabies viruses circulating in China.

A CpG oligodeoxynucleotide enhances the immune response to rabies vaccination in mice.

BACKGROUND: Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models. METHODS: A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP. RESULTS: HDCV combined with CpG ODN (HDCV-CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV-1.25 µg CpG or HDCV-5 µg CpG increased the levels of RVNA. In particular, 5 µg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 µg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV-CpG survived, while the survival rate of mice immunized with HDCV alone was 30%. CONCLUSIONS: The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.

Intranasal vaccination with ebola virus GP amino acids 258-601 protects mice against lethal challenge.

Ebola virus (EBOV) disease (EVD) leads to lethal hemorrhagic fever with a case fatality rate as high as 90%, thus posing a serious global public health concern. However, while several vaccines based on the EBOV glycoprotein have been confirmed to be effective in animal experiments, no licensed vaccines or effective treatments have been approved since the first outbreak was reported in 1976. In this study, we prepared the extracellular domain of the EBOV GP protein (designated as N20) by prokaryotic expression and purification via chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we evaluated the immunogenicity of N20 by intranasal administration and the associated protective efficacy against mouse-adapted EBOV challenge in mice. We found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on IgG subclasses and IFN-γ/IL-4 secreting cells; and mucosal immunity, based on the presence of anti-EBOV IgA in vaginal lavages. We also confirmed that the vaccine could completely protect mice against a lethal mouse-adapted EBOV (MA-EBOV) challenge with few side effects (based on weight loss). In comparison, mice that received N20 or H45 alone succumbed to lethal MA-EBOV challenge. Therefore, mucosal vaccination with H45-adjuvanted N20 represents a potential vaccine candidate for the prevention of EBOV in an effective, safe, and convenient manner.

Rabies virus transmission via solid organs or tissue allotransplantation.

BACKGROUND: Rabies, for which the mortality rate is almost 100%, is a zoonotic viral disease that can be transmitted via solid organs or tissue allotransplantation. Dozens of deaths from rabies via solid organs or tissues allotransplantation (ROTA) have been documented during the last decades. In 2015 and 2016, two cases of rabies virus transmission via solid organs or tissue allotransplantation were reported in China, which further underscore the risk and importance of this special type of rabies for organ transplant recipients. MAIN TEXT: From 1978 to 2017, at least 13 cases of ROTA, causing dozens of deaths, have been reported worldwide, whether in the high-risk or low-risk countries of rabies. The reported incubation period of ROTA ranges from 11 days to more than 17 months, while the historical incubation period of rabies is generally considered to range from ~ 1 week to several years. The pathogenesis of ROTA is not clear, but the use of post-exposure prophylaxis (PEP) can play a protective role in the transplant recipients. We also summarize reports about ROTA in China, combined with the actual situation regarding work on rabies surveillance and elimination, and suggest countermeasures for the prevention and control of ROTA in the future. CONCLUSIONS: Understanding the significance of ROTA, screening the suspected organs, assessing the risk and protecting the related population will be effective way to prevent and control further occurrence of ROTA.

Clinical and pathological features of patients with biliary atresia who survived for more than 5 years with native liver.

PURPOSE: The objective of this study was to determine the predictive index for prognosis in patients with biliary atresia (BA). METHODS: A total of 71 patients were divided into two groups. Group A included 39 postoperative BA patients who survived for more than 5 years with normal liver function and did not present cirrhosis, and group B included 32 patients who died from liver failure within 1 year after surgery. The clinical data of the two study groups were compared, and liver pathology was evaluated using a scoring system. RESULTS: The average age and weight were similar in the two groups (64.1 ± 16.8 days vs. 60.7 ± 19.3 days, p > 0.05; 4.9 ± 0.9 kg vs. 4.7 ± 0.8 kg, p > 0.05). There were no significant intergroup differences in preoperative total bilirubin (TB), direct bilirubin (DB), alanine transaminase, aspartate transaminase, and international normalized ratio. The preoperative levels of gamma-glutamyl transpeptidase (γ-GT) and albumin in group A were significantly higher than those in group B (γ-GT: 956.8 ± 503.8 IU/L vs. 620.2 ± 437.1 IU/L, p = 0.00; ALB: 40.8 ± 2.5 g/L vs. 36.8 ± 3.6 g/L, p = 0.04), whereas alkaline phosphatase was significantly lower in group A compared to group B (512.2 ± 224.6 IU/L vs. 631.7 ± 254.7 IU/L, p = 0.02). The postoperative TB and DB after 2 weeks of the Kasai procedure decreased significantly more in group A than in group B (TB: 53.9 vs. 21.4%, p = 0.00; DB: 51.0 vs. 22.7%, p = 0.00), whereas γ-GT increased significantly less in group A than in group B (48.3 vs. 142.1%, p = 0.00). Cystic structures were observed at the porta hepatis on ultrasound in more patients from group A (28.2 vs. 3.2%, p < 0.00). There was no significant difference in the total pathological score between the two groups (p = 0.38) whereas the score of bile plugs was significantly higher in group A (0.95 vs. 0.38, p = 0.03). CONCLUSION: The cystic structures observed at the porta hepatis on ultrasound preoperatively and the rapid decrease in TB and DB within 2 weeks postoperatively predict good long-term prognosis, whereas a significant increase in γ-GT with a lower preoperative level predicts poor long-term prognosis. The development of bile plugs may be an indicator of favorable prognosis.

MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease.

MicroRNAs (miRNAs), one kind of post-transcriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson's disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson's disease. It even considers miRNAs as a potential target for Parkinson's disease therapy.

Role of systemic injection of rabies immunoglobulin in rabies vaccination.

To determine the role of systemic injection of rabies immunoglobulin (RIG) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of RIG combined with rabies vaccine. Our results indicate that systemic injection of RIG does not contribute detectably to passive or adaptive immunization, suggesting that the main function of RIG in individuals with category III exposure is to neutralize rabies virus via immediate local infiltration of the wound.

Hypersplenism Associated With Late-Presenting Congenital Diaphragmatic Hernia: A Rare Combination. Case Report.

Congenital diaphragmatic hernia (CDH) is a rare developmental anomaly of the diaphragm that mainly presents mainly in newborns. Even less common is late-onset CDH associated with hypersplenism. We report a 10-year-old male who presented with coughing, blood-stained sputum, and fever. He was diagnosed with CDH complicating hypersplenism after computed tomography was done. The patient was treated by CDH repair and splenectomy, and remained asymptomatic at 6-month follow-up. Computed tomography can be an important diagnostic option in this rare combination of CDH and hypersplenism, and surgical intervention is strongly recommended.