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This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [ M ( Q 1 , Q 3 )]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [ M ( Q 1 , Q 3 )]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

Ferroptosis is a kind of iron-dependent renewal programmed death. Its main mechanism is to catalyze the unsaturated fatty acids highly expressed on the cell membrane under the effect of divalent iron, to produce lipid peroxidation, thus inducing cell death. SLC7A11 is a known iron death-related factor. It has been proved that iron death is involved in the occurrence and development of acute diseases, but the specific mechanism is unknown. The purpose of this review is to highlight the regulatory properties of SLC7A11 and gain a deeper understanding of its role in ferroptosis-related acute injury diseases. This is a narrative review. PubMed was used as the main source to randomly implement literature search strategy to index Scopus articles. No specific terms are used. Studies have shown that SLC7A11 may affect the sensitivity of cells to iron ptosis by regulating it at the transcriptional or post-transcriptional level, which is related to the pathology of many acute injury diseases, such as acute lung injury (ALI), acute kidney injury (AKI), acute liver injury, myocardial ischemia-reperfusion injury, and acute cerebral hemorrhage. In order to clarify this point, more and more researchers turn their attention to the study of the specific mechanism between SLC7A11 and ferroptosis-related acute injury diseases. In summary, this review summarized some specific mechanisms by which ferroptosis could be controlled by SLC7A11 and clarified the underlying mechanisms of a series of diseases caused by SLC7A11-associated ferroptosis. It also provided more scientific justification for the clinical application of targeting ferroptosis in preventing and treating various diseases.

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

Objective: To understand the characteristics and associated factors of viral nucleic acid conversion in children infected with Omicron variant strain of SARS-CoV-2 in Shanghai. Methods: The clinical symptoms, laboratory results and other data of 177 children infected with SARS-CoV-2 who were hospitalized in Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (designated hospital for SARS-CoV-2 infection in Shanghai) from April 25 to June 8, 2022 were retrospectively analyzed. According to the chest imaging findings, the children were divided into mild and common type groups. According to their age, the unvaccinated children were divided into<3 years old group and 3-<18 years old group. According to the vaccination status, the children aged 3-<18 year were divided into non-vaccination group, 1-dose vaccination group and 2-dose vaccination group. Comparison between groups was performed by independent sample t -test and analysis of variance, and multivariate linear regression analysis was used for multivariate analysis. Results: Among the 177 children infected with Omicron variant of SARS-CoV-2, 96 were males and 81 were females, aged 3 (1, 6) years. The time of viral nucleic acid negative conversion was (10.3±3.1) days. The 177 children were 138 cases of mild type and 39 cases of common type. Among the children aged 3-<18 years old, 55 cases were not vaccinated, 5 cases received 1-dose and 36 cases received 2-dose vaccination. Among the 36 children who received 2 doses of vaccination, the time of viral nucleic acid negative conversion was shorter in those vaccinated within 6 months than those over 6 months ((7.1±1.9) vs. (10.8±3.0) d, t= -3.23, P= 0.004). Univariate analysis showed that the time of nucleic acid negative conversion of SARS-CoV-2 was associated with age, underlying diseases, gastrointestinal symptoms, white blood cell count, proportion of neutrophils, proportion of lymphocytes, and the number of doses of SARS-CoV-2 vaccine ( t =3.87, 2.55, 2.04, 4.24, 3.51, 2.92, F =16.27, all P <0.05). Multiple linear regression analysis showed that older age (β=-0.33, 95% CI -0.485--0.182, P <0.001) and more doses of vaccination (β=-0.79, 95% CI -1.463--0.120, P= 0.021) were associated with shortened nucleic acid negative conversion time in children, while lower lymphocyte proportion (β=-0.02, 95% CI -0.044--0.002, P= 0.031) and underlying diseases (β=1.52, 95% CI 0.363-2.672, P= 0.010) were associated with prolonged nucleic acid negative conversion time in children. Conclusion: The children infected with Omicron variant of SARS-CoV-2 with reduced lymphocyte proportion and underlying diseases may have longer time of viral nucleic acid negative conversion,while children with older age and more doses of vaccination may have shorter time of viral nucleic acid negative conversion.

Panax notoginseng round spot disease (PRSD), caused by Mycocentrospora acerina , is the main leaf disease occurring in cultured P. notoginseng . Aiming to find a safe and efficient control method for PRSD, we studied the disease characteristics of PRSD and the optimal growth conditions of M. acerina and evaluated the efficacy of rain-shelter cultivation in PRSD control. Moreover, we described M. acerina based on morphological characterization and molecular analyses (ITS, ACT , LSU , and TEF-1α ). The optimum temperature for M. acerina conidial germination was found to be 14 to 22°C. Furthermore, leaf surface wetness for at least 4 h is required for conidial germination, and conidia can successfully infect P. notoginseng when the leaf wetness lasts for more than 8 h. Additionally, rainwater splashing determines the conidial transfection distance, which is less than 2 m. Finally, our study revealed that rain-shelter cultivation is an effective and simple physical prevention strategy to control PRSD, with an average efficacy of up to 100%.

Objective: To investigate whether the contralateral normal external auditory canal (EAC) skin graft can maintain the ear canal health after EAC reconstruction in unilateral congenital aural atresia (CAA) cases. Methods: A Zelen design randomized controlled study was used to collect unilateral CAA patients for EAC reconstruction prospectively (clinical trial registration number: ChiCTR2000032103). The patients were randomly divided into the control group and the trial group. The trial group used the contralateral normal EAC skin graft group (transplant part of the contralateral normal EAC skin to repair the atresia side for unilateral CAA patients), the control group all used scalp blade thick skin. We observed the EAC health and hearing results of the two groups after EAC reconstruction. Results: A total of 13 cases were enrolled from July 2020 to August 2021. There were eight patients in the trial group, including six males and two females, with an average age of 22.3 years (14-36 years). There were two patients with CAA on the left and six patients on the right. The average follow-up time was 8.8 months (4-14 months). There were five patients in the control group, all cases were male with an average age of 16.2 years (12-20 years). There were four patients with CAA on the left and one patient on the right. The average follow-up time was 7.0 months (2-14 months). In the trial group, eight cases of reconstructed EAC epithelium were healthy, one patient had cicatricial stenosis of EAC opening and lateralization of the tympanic membrane. The other patient had cicatricial stenosis of reconstructed EAC, this case also had scar hyperplasia of the contralateral EAC opening but recovered after soft packing and triamcinolone acetonide injection treatment. The healthy side EAC of the rest trial group had no scarring stenosis or local bone hyperplasia during long-term follow-up. In the control group, one patient was lost to follow-up and the other four patients had dry ears of reconstructed EAC, but easily to form crusts and needed to be cleaned repeatedly, one patient had lateralization of the tympanic membrane, the EAC epithelium was not healthy for long-term follow-up. The incidence of complications related to EAC reconstruction was lower than previous studies ( χ²= 5.55, P =0.018), and the average postoperative Air-Bone Gap increased (18.8±10.0)dB. Conclusion: By optimizing the EAC reconstruction technology, the health of the reconstructed EAC is improved compared with the previous study. After active intervention and treatment, there should be no scarring stenosis or local bone hyperplasia on the contralateral side EAC.

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval( CI ): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95% CI : 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95% CI : 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95% CI : 0.51-1.40; DSS: aHR: 0.62, 95% CI : 0.35-1.11; DFS: aHR: 0.80, 95% CI : 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

Objective: To discuss the challenges and problems of the prevention and control of emerging infectious diseases in Shanghai as a megacities. Methods: An imported case of cutaneous anthrax occurred in Shanghai on May 30, 2019. Shanghai Municipal Center for Disease Control & Prevention conducted an epidemiological investigation and treatment of the cases; after this case, the data of patients with cutaneous anthrax were collected, and an epidemiological study was conducted. Meanwhile, the wound and blood samples of the patient were collected for laboratory testing. Results: Of the seven wound samples of the patient, 6 were positive for the Bacillus anthracis nucleic acid test, and the double serological test results showed a 4-fold increase in the titer of anthrax antibodies. Shanghai CDC conducted an epidemiological investigation of the confirmed cases and observed its contacts. After treatment, the patients recovered, and no other issues appeared among the 19 contacts. Conclusions: Shanghai must strengthen the training of clinicians on emerging infectious diseases to achieve early detection, diagnosis, and treatment of imported infectious diseases and reduce the incidence, spread, and death of the diseases. At the same time, multi-department joint prevention and control are needed to prevent and control secondary cases.

Objective: To investigate the effects of topical administration of cyclosporine A (CsA) on salivary secretion and inflammation of the submandibular glands in non-obese diabetic (NOD) mice., Methods: Female NOD mice, 21 aged 14 weeks and 18 aged 21 weeks were selected and randomly divided into low-dose group, high-dose group and control group on average. CsA was injected into submandibular glands. One week later the saliva stimulated by pilocarpine was collected and measured. The submandibular glands were collected to make paraffin sections. The lymphocyte infiltration in submandi-bular gland was observed by microscope after hematoxylin-eosin (HE) staining. The number of lymphocyte infiltration foci was counted to calculate the focus sore and the ratio of lymphocyte infiltration area to total gland area was figured up by Leica image analysis system. The expressions of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-13, IL-17F, IL22 and IL-23a in the submandibular glands of the NOD mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis in the submandibular gland was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and γ-glutamyl transferase (GGT) were measured by automatic biochemical analyzer to evaluate liver and kidney functions., Results: After topical injection of CsA in the submandibular gland, the stimulated salivary flow rate of the 14- and 21-week-old NOD mice significantly increased compared with the control group ( P < 0.01 or P < 0.05), and the number and area of lymphocyte infiltration foci in the 14-week-old NOD mice low-dose group significantly decreased compared with the control group ( P < 0.01). Low and high dose of CsA had similar effects on reducing inflammation and improving salivary secretion. The overall level of inflammatory cytokines in the submandibular gland did not decrease significantly. The number of cell apoptosis of submandibular gland in the NOD mice treated with CsA decreased compared with the control group, but there was no statistically significant difference. Topical injection of CsA had no adverse effect on liver and kidney function in the NOD mice., Conclusion: Topical injection of CsA can reduce lymphocyte infiltration in submandibular gland of NOD mice and improve salivary secretion.

Objective: To investigate the clinical value of dual-channel contrast-enhanced ultrasound (DCUS) in the classification of hilar cholangiocarcinoma and the diagnosis of the etiology of low obstructive jaundice. Methods: The data of 114 patients with obstructive jaundice examined by the Department of Ultrasound of Lanzhou University Second Hospital from October 2018 to February 2020 were retrospectively collected. There were 60 males and 54 females, aged 37~84 (63±10) years. All patients underwent preoperative transvenous contrast-enhanced ultrasound (CEUS), intraoperative puncture needles, postoperative ultrasound-guided percutaneous transhepatic cholangiocarcinography (UG-PTC) and three-dimensional ultrasound cholangiography (3D-USC) through an external drainage tube, known as DCUS. The classification of hilar cholangiocarcinoma and the nature of low biliary tract obstruction were determined according to the characteristics of DCUS images. All patients who have received DCUS underwent magnetic resonance cholangiopancreatography (MRCP) and X-ray cholangiography. X-ray cholangiography was used as the gold standard for classification of hilar cholangiocarcinoma, and the accuracy of US, CEUS and DCUs was analyzed. Low obstructive jaundice was characterized by surgical pathology as the gold standard, and the diagnostic efficacy of conventional ultrasound (US), CEUS and DCUs was analyzed. At the same time, the receiver operating characteristic (ROC) curve was used to compare the efficacy of MRI+MRCP and DCUS in determination of the nature of low biliary obstruction. Results: The coincidence rates of US, CEUS, and DCUS in the classification of hilar cholangiocarcinoma and X-ray cholangiography were: 75.6% (34/45), 82.2% (37/45), and 93.3% (42/45), respectively. The coincidence rates of US, CEUS, and DCUS in the determination of the nature of low biliary obstruction and surgical pathology were 56.5% (39/69), 82.6% (57/69), and 85.5% (59/69), respectively. Compared with conventional ultrasound, CEUS had no statistically significant difference in the diagnosis of hilar cholangiocarcinoma ( P =0.438), and DCUS had statistically significant difference in the diagnosis of hilar cholangiocarcinoma ( P =0.039).ROC curve analysis suggested that the cut-off value of MRI+MRCP grade and DCUS grade for diagnosing benign and malignant low biliary obstruction were both 2.5; the area under the curve (AUC) were 0.897 and 0.906, respectively (both P <0.01); sensitivity were 77.5% and 93.1%, respectively; and the specificity were 87.5% and 82.8%, respectively. Conclusion: The value of DCUS in the classification of hilar cholangiocarcinoma and the qualitative diagnosis of low biliary tract obstruction was comparable to that of X-ray cholangiography and MRCP. DCUS had important clinical application value in the classification of hilar cholangiocarcinoma and the etiological diagnosis of low obstructive jaundice.

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.

Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective: To identify the epidemic clones of MRSA isolates at a hospital in shanghai. Methods: A total of 72 MRSA isolates have been isolated from a second grade hospital between 2017 and 2018, including 32 CA-MRSA isolates, 13 HA-MRSA isolates and 26 MRSA isolates from environment. In this study, MLST and PFGE typing methods were used to analyze the molecular epidemiology of the MRSA isolates. Results: A total of 72 MRSA isolates have been obtained including 46 isolates from clinical specimens, 26 isolates from environments. The 46 MRSA isolates from clinical specimens consisted of 33 CA-MRSA (community-acquired MRSA) and 13 HA-MRSA (hospital-acquired MRSA). Furthermore, these patients infected with MRSA isolates were mostly distributed in the department of geriatrics (34.8%, 16/46), internal medicine (26.1%, 12/46) and surgery (26.1%, 12/46). MLST typing results showed that ST764 was predominant in isolates from both clinical specimens and hospital environments. Furthermore, PFGE typing results showed that most ST764 MRSA had high homolog (>90%). Conclusion: ST764 MRSA isolates might spread in community, hospital and environments. Therefore, continuous monitoring of MRSA and its variation may be useful in understanding the involvement of epidemic clone, and in searching new strategies to control MRSA infection.

The circadian clock is a generator of self-sustaining physiological and behavioral rhythms, which can be guided by external environmental factors, so as to synchronize biological behaviors with external environmental changes. The modern lifestyles make the human body incapable of synchronization to the external time with the circadian rhythm, and thus form a social jet lag. Non-alcoholic fatty liver disease (NAFLD) is a disorder closely related to metabolic abnormalities. The circadian clock is closely related to metabolic abnormalities and NAFLD and changes among them may be involved with feeding mode and ingredients, sleeping time, and intestinal flora. Molecules associated with the circadian clock are expected to become potential drugs for the treatment of NAFLD. This article mainly reviews the latest research progress of circadian clock and NAFLD.

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups ( P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups ( P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

Objective: To summarize the clinical features, diagnosis and treatment of mucosa-associated lymphoid tissue(MALT) lymphoma in head and neck. Method: The clinical data of 22 hospitalizedpatients with MALT lymphoma in head and neck during the recent 18 years were analyzed retrospectively. Result: Among the 22 cases, 13 patients showed salivary gland lesions, 4 showed larynx and trachea lesions,3 showed nasopharynx lesions and 2 showed thyroid gland lesions. The clinical manifestation was occupying or compression. Among them,12 patients received chemotherapy or chemoradiotherapy,5 received surgery plus chemotherapy,3 received surgery plus radiotherapy, 1 received surgery alone and 1 received radiotherapy alone; complete response(CR) occurred in 15 patients, partial response(PR) occurred in 6 patients, and 1 was stable disease(SD). The mean follow-up time was 92(8-211) months. During the follow-up period, 18 patients survived, 4 died, the three year progression free survival(PFS) and overall survival(OS) were both 95.2%, and the fiveyear PFS and OS were 79.4% and 89.6% respectively. Conclusion: The prognosis of MALT lymphoma in head and neck was good. MALT lymphoma has no specific clinical manifestations. Chemotherapy was the main treatment. Local treatment can be conducted for patients with localized lesions. ., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ (2)=4.086, P =0.043; 53.8% (7/13) vs 87.5% (56/64) , χ (2)=9.766, P =0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P =0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT ( P =0.558, P =0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group ( P =0.049, P =0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS ( P =0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation ( P =0.114, P =0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Objective: To summarize the clinical characteristics of congenital pyriform fistula with acute suppurative thyroiditis as the initial presentation. Method: A total of 71 patients with congenital pyriform sinus fistula were treated, of which 33 cases had acute suppurative thyroiditis as the first symptom. For the patients with congenital pyriform sinus fistula who have acute suppurative thyroiditis as the first symptom, infection should be controlled first. Full drainage should be done when necessary, and the lesion should be completely excised during the stable period. Result: All the patients were followed up for 6 months to 216 months. No recurrence was found during follow-up. Conclusion: For patients with acute suppurative thyroiditis, the possibility of congenital pyriform sinus fistula should be considered.If the diagnosis of congenital pyriform sinus fistula is clear,the lesion should be completely resected by surgery. ., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Due to immature development of the immune system, preterm infants are at increased risk of infections from vaccine-preventable diseases. But at the same time, premature vaccination may not induce a good immune response because of the incomplete development of the neonatal immune system, and may cause serious adverse reactions risk due to the poor immune tolerance, thus vaccination of preterm infants at the appropriate time is the key to reducing the risk of infectious disease and obtaining vaccine protection. At present, it is generally recommended that the gestational age and birth weight should be considered in the vaccination of preterm infants. The timing, type and even the immunization schedule of the vaccine should be differ from that of the full term infants. However, there is a lack of research results and data on immunization program in preterm infants in China, and there is still no provided universal guidelines for their vaccine immunization. This article aims to summarize the guidelines and clinical trials of vaccination of preterm infants in foreign countries, and to provide reference for the formulation and implementation of immunization strategies for preterm infants in China.

Objective: To investigate the effects of inhibiting glutaredoxin 3(GLRX3) expression on proliferation and apoptosis of lung cancer cells. Methods: Western blotting was used to detect the expressions of GLRX3 protein in human embryonic lung fibroblast MRC5 and lung cancer cells, including A427, A549, PC9 and H1299. GLRX3-targeted siRNA (experimental group) and negative siRNA (negative group) were transfected into A549 cells, and the cells without special treatment were blank group. The protein expression levels of GLRX3, cleaved cysteinyl aspartate specific proteinase 3(cleaved caspase-3), signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3) in each group at 48 hours after transfection were measured by Western blotting. The proliferation ability of differently treated cells at 24 hours, 48 hours and 72 hours after transfection were detected by CCK-8 array. The cell apoptosis at 48 hours after transfection was evaluated by flow cytometry. Results: The protein expression levels of GLRX3 in MRC5, A427, A549, PC9 and H1299 were 0.094±0.010, 0.282±0.021, 0.551±0.045, 0.423±0.039 and 0.454±0.036, respectively. The protein expressions of GLRX3 in tested lung cancer cells were significantly higher than that of MRC5 cells (all P <0.01). The GLRX3 protein expressions in blank group, negative control group and experimental group at 48 hours after transfection were 0.311±0.029, 0.328±0.032 and 0.103±0.012, respectively. GLRX3 protein expression level of experimental group in A549 cells was significantly lower than that of control group ( P <0.01), whilewithout statistical difference between the negative group and blank group ( P >0.05). A values of experimental group at 24, 48 and 72 hours after transfection in A549 cells were significantly different from those of blank group (all P <0.01). Percent of apoptotic cells in the experimental group was (9.52±0.56)%, which was significantly higher than that of blank group [(1.65±0.22)%] and negative control group [(1.42±0.26)%, all P <0.01]. Consistently, compared with blank group, the cleaved caspase-3 markedly increased in the experimental group ( P <0.01). The protein expression of p-STAT3 in the experimental group was significantly lower than the blank group ( P <0.01), while no significant difference of STAT3 protein expression was observed among all the groups ( P >0.05). Conclusions: Inhibition of GLRX3 gene expression can inhibit the proliferation of lung cancer cells and induce cell apoptosis through up-regulating cleaved caspase-3 expression and down-regulating STAT3 signaling pathway.

Objective: To investigate both the relationship and underlying mechanism between miR-30a and migraine., Patients and Methods: Peripheral blood samples were collected from migraine patients and healthy people to extract RNA for quantitative Real-time PCR (qRT-PCR). The relationship between mRNA expressions and patient data was analyzed by t-test. Target genes of miR-30a were predicted by the TargetScan. The binding of miR-30a to the target gene was verified by dual fluorescein reporter assay. The protein expression of calcitonin/alpha-CGRP gene (CALCA), the miR-30a target gene, was detected by Western blot., Results: Expression levels of miR-30a in peripheral blood of migraine patients were significantly lower than those of healthy controls detected by qRT-PCR, and the methylation level of miR-30a in promoter region was remarkably increased. In addition, expression levels of miR-30a were significantly decreased in patients with bilateral seizures, persistent pain and high pain index. CALCA was found to be the target gene of miR-30a via bioinformatics analysis. We verified that miR-30a degrades CALCA by dual-luciferase reporter assay. Western blot results showed that overexpression of miR-30a down-regulated the CALCA expression, and knockdown of miR-30a upregulated the CALCA expression., Conclusions: Expression levels of miR-30a are significantly decreased in migraine patients and can relieve migraine through the degradation of CALCA.

Objective: To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients with partial response after a standard course of interferon therapy. Methods: A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy (48-60 weeks) from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type. Results: A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group (22.6%/29.0% vs 0%/3.7%, P < 0.05). At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group (22.6% vs 0%, P = 0.015). Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation. Conclusion: In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.

Objective: To investigate the effects of Toll like receptors on the osteogenesis of human pe-riodontal ligament stem cells (hPDLSCs) and probable molecular mechanism., Methods: Real-time PCR and flow cytometry were applied to test the expression of TLRs in hPDLSCs and the positive cell percentage of TLR. hPDLSCs were cultured in osteogenic medium for 7 to 14 days with different TLR agonists at various concentrations . The effect of different TLR on osteogenic differentiation of hPDLSCs was evaluated by alizarin red S staining, alkaline phosphatase (ALP) staining and ALP activity assay. Western blotting was used to analyze the phosphorylation levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal protein kinase (JNK), P38, AKT and expression of Runx2 an osteogenic related gene after treatment with TLR agonists, compared with the effect of inhibitors of mitogen activated protein kinase (MAPK) or protein kinase B (PKB or AKT) on Runx2 expression of hPDLSCs cultured in osteogenic medium., Results: Higher expressions of TLR1,3,4,6 were found in hPDLSCs through real-time PCR. Positive cell percentage of TLR was determined by flow cytometry and described as TLR1: 2.82%±0.68%; TLR2: 1.26%±0.09%; TLR3: 13.23%±2.05%; TLR4: 3.64%±0.79%; TLR6: 3.21%±1.64%, whose tendency was comparable to their mRNA expression in hPDLSCs. Most TLR ligands had no effect on the ALP staining, activity and mineralization of hPDLSCs at lower concentration except for 0.1 mg/L PolyI:C could induce the osteogenic ability of hPDLSCs. On the contrary, Higher concentration of TLR ligands (PolyI:C: 10 mg/L, LPS: 10 mg/L , Pam3CSK4: 1 mg/L, FSL-1: 50 μg/L) had obviously inhibitory effect on osteogenic differentiation of hPDLSCs. Activation of TLR using higher concentration of TLR ligands could downregulate the phosphorylation levels of ERK, P38, JNK and AKT, and also reduced the expression of Runx2, compared with the untreated control. The inhibitors of MAPK (U0126, SP600125,SB203580) and inhibitor of AKT (perifosine) could also inhibit Runx2 expression., Conclusion: Higher concentration of TLR ligands could inhibit osteogenic differentiation of hPDLSCs. This inhibitory effect seemed to be related to decreased phosphorylation of MAPK and AKT.

This cross-sectional study investigated the association between the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and bone mineral density in Chinese adults. We found that better adherence to the AHA-DLR associated with higher bone mineral density (BMD) at multiple sites., Introduction: Accumulating evidence shows that cardiovascular disease (CVD) and osteoporosis are associated with each other, yet little research has focused on whether strategies to reduce CVD risk could also benefit bone health. We aimed to assess the association between adherence to the modified 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) and BMD in Chinese adults., Methods: We included 2092 women and 1051 men aged 40-75 years in this community-based cross-sectional study. Dietary information was assessed using a 79-item food frequency survey through face-to-face interviews at baseline (2008-2010) and 3 years later (2011-2013). Adherence to the AHA-DLR was assessed using modified diet and lifestyle scores (American Heart Association Diet and Lifestyle Score (AHA-DLS)) adjusted for bone health. BMD for the whole body, lumbar spine, total hip, femur neck, and trochanter sites was measured using dual-energy X-ray absorptiometry in 2011-2013., Results: After adjusting for potential covariates, greater adherence to the modified AHA-DLS was positively and dose-dependently associated with BMD. The mean BMD was 1.93-3.11% higher in quartile 4 (vs. 1) (all p values <0.01) at multiple sites. Five-unit increases in the modified AHA-DLS score were associated with 4.20-6.07, 4.44-8.51, and 3.36-4.67 mg/cm 2 increases in BMD at multiple sites for the total subjects, males, and females, respectively (all p values <0.01)., Conclusions: Better adherence to the AHA-DLR shows protective associations with BMD at multiple sites in the middle-aged and elderly Chinese population.

NACHT-LRR-PYD-containing proteins 3 (NLRP3) inflammasome regulates the maturation and secretion of proinflammatory cytokines including interleukin-1β and interleukin-18, as well as immune and inflammatory response, through the activation of cysteine aspartate specific protease-1. Inflammatory response caused by the activation of NLRP3 inflammasome may participate in the development and progression of nonalcoholic fatty liver disease (NAFLD). Therefore, exploration of the role of NLRP3 inflammasome in NAFLD is important for the understanding of the pathogenesis of NAFLD and discovery of new therapeutic targets.

B*44:237N differs from B*44:03:01 by nucleotides deletion at nucleotide 286 and 287 in exon 2., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Damage-associated molecular patterns (DAMPs) are a series of intracellular molecules with immunoregulatory activity which are released by the damaged or activated cells and can induce autoimmunity or immune tolerance via pattern recognition receptors. At present, the DAMPs which have been discovered include extracellular histone, high-mobility group box-1, chromosomal deoxyribonucleic acid, interleukin-18, interleukin-32, uric acid, and mitochondrial transcription factors. The discovery of DAMPs and clarification of their mechanisms of action help to know the pathophysiological process of liver failure and provide new thoughts for the diagnosis, prevention, and treatment of liver failure. This article briefly summarizes the concept of DAMPs and their mechanisms of action in the development and progression of liver failure.

HLA-B*40:01:47 differs from HLA-B*40:01:01 by one nucleotide exchange at position 420 in exon 3., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this study, the full-length complementary (c)DNA of common carp Cyprinus carpio melanoma differentiation-associated gene 5 (mda5) was cloned. The complete open reading frame of C. carpio mda5 contained 2982 bp and encodes 993 amino acids. The deduced amino acids contained six functional domains: two caspase activation and recruitment domains (CARD), a conserved restriction domain of bacterial type III restriction enzyme (ResIII), a DExD/H box-containing domain (DEXDc), a helicase super family C-terminal domain (HELICc) and a C-terminal regulatory domain (RD). The mda5 gene was expressed in all tested tissues, with high levels in the gills and spleen, while lower expressed in gonad and blood. The copy numbers of mda5 were increased in the liver, spleen, head kidney and the mucosal-associated immune tissues such as the foregut, hindgut, gills and skin after stimulation with polyinosinic polycytidylic [poly(I:C)] and Aeromonas hydrophila. The myxovirus resistance gene (mx) messenger (m)RNA levels in the spleen, head kidney, foregut and gills were significantly up-regulated after poly(I:C) injection. When injected with poly(I:C), mda5 and mx transcripts were also significantly induced in vitro. These results implied that mda5 might be involved in both antiviral and antibacterial innate immune processes in C. carpio. © 2016 The Authors. Journal of Fish Biology © 2016 The Fisheries Society of the British Isles., (© 2016 The Fisheries Society of the British Isles.)

Objective: To analyze the differences of coronary artery anomalies between Han and Tibetan nationality living in middle and high altitude., Methods: A total of 7 028 adults living in the Qinghai Plateau(1 800-7 720 m altitude), who underwent coronary CT angiography in Qinghai Cardio-cerebro-vascular Disease Special Hospital between 2010 to 2015, were included in this study.There were 6 391 cases of the Han nationality and 637 cases of the Tibetan nationality. The differences of coronary artery anomalies between Han and Tibetan nationality were analyzed retrospectively., Results: (1) Incidence of coronary artery anomalies was lower in Han nationality than in the Tibetan nationality (1.596%(102/6 391)vs. 4.239%(27/637), P<0.001). (2) There was 64.7%(66/102) male residents with coronary artery anomalies in Han nationality, and 74.1% (20/27) male residents with coronary artery anomalies in Tibetan nationality(P=0.359). (3) Left side coronary artery anomalies in Han nationality was similar as in Tibetan nationality (64.4%(67/104) vs. 55.6%(15/27), P=0.396). (4) Incidence of benign coronary artery anomalies was significantly lower in Han nationality than in Tibetan nationality (0.720%(46/6 391) vs. 2.200%(14/637), P<0.001). Incidence of potentially dangerous coronary artery anomalies was also significantly lower in Han nationality than in Tibetan nationality (0.876%(56/6 391) vs. 2.041%(13/637), P=0.004). (5)Ten kinds of coronary artery anomalies were found in this study. There were significant differences between Han and Tibetan nationality in left coronary artery originated from right coronary sinus(0.046%(3/6 391) vs. 0.471%(3/637), P=0.012), in left circumflex branch originated from right coronary sinus(0.046%(3/6 391)vs. 0.471%(3/637), P=0.012), and opening of right coronary artery in left coronary sinus or left anterior descending(0.704%(45/6 391)vs. 1.570%(10/637), P=0.018)., Conclusion: The incidences of coronary artery anomalies and benign coronary artery anomalies were significantly lower in Han nationality residents than that of the in Tibetan nationality residents living in middle and high altitude.

HLA-A*24:02:96 shows one nucleotide difference from HLA-A*24:02:01:01 at position 318 in exon 2 from C to T., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*55:77 differs from B*55:02:01:01 by a single nucleotide at position 164 in exon 2., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

N-Doped carbon materials are promising candidates as alternative catalysts to noble metals in promoting the oxygen reduction reaction (ORR) in fuel cells. However, methods to further reduce the ORR overpotential and improve related kinetics remain to be developed. This study reports that N-doped graphene frameworks (NGFs) synthesized from the rapid pyrolysis of solid glycine particles in the presence of sodium carbonate, display an extremely large specific surface area (1760 m(2) g(-1)) and a graphitic-N-dominant C-N configuration. The NGFs can efficiently catalyze the electrochemical reduction of molecular oxygen into water following a 4e pathway, with a low overpotential (0.98 V of onset potential vs. RHE), very high kinetic limiting current density (16.06 mA cm(-2)), and turnover frequency (121 s(-1)), much better than the commercial Pt/C catalyst.

The new allele, HLA-B*40:324 differs from B*40:63 by two nucleotide changes in exon 3., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*11:152 differs from A*11:01:01 by a single nucleotide at position 266 in Exon 2., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Powdery mildew and rust fungi are obligate parasites that cannot live without host organisms. They are difficult to culture in synthetic medium in the laboratory. Genomic DNA extraction is one of the basic molecular techniques used to study the genetic structure of populations. In this study, 2 different DNA extraction methods, Chelex-100 and cetyltrimethylammonium bromide (CTAB), were used to extract DNA from euonymus powdery mildew and Puccinia striiformis f. sp Tritici. Polymerase chain reaction was carried out with a race-specific-marker rDNA-internal transcribed spacer sequence. Both DNA extraction methods were compared and analyzed. The results showed that both Chelex-100 and CTAB were effective for extracting genomic DNA from infected plant tissue. However, less DNA was required for the Chelex-100 method than for the CTAB method, and the Chelex-100 method involved fewer steps, was simpler and safer, and did not require organic solvents compared to the CTAB method. DNA quality was evaluated by polymerase chain reaction, and the results showed that genomic DNA extracted using the Chelex-100 method was better than that using CTAB method, and was sufficient for studying the genetic structure of population.

The binding interaction of lovastatin with calf thymus DNA (ct-DNA) was studied using UV/Vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results showed that there was an obvious binding interaction of lovastatin with ct-DNA and the binding constant (Kb ) was 5.60 × 10(3) M(-1) at 298 K. In the binding process of lovastatin with ct-DNA, the enthalpy change (ΔH(0)) and entropy change (ΔS(0)) were -24.9 kJ/mol and -12.0 J/mol/K, respectively, indicating that the main binding interaction forces were van der Waal's force and hydrogen bonding. The molecular docking results suggested that lovastatin preferred to bind on the minor groove of different B-DNA fragments and the conformation change of lovastatin in the lovastatin-DNA complex was obviously observed, implying that the flexibility of lovastatin molecule plays an important role in the formation of the stable lovastatin-ct-DNA complex., (Copyright © 2015 John Wiley & Sons, Ltd.)

In this study, the full-length complementary (c)DNA of interleukin-1 receptor-associated kinase 1 gene (irak1) was cloned from common carp Cyprinus carpio. The complete open reading frame of irak1 contained 2109 bp encoding a protein of 702 amino acid residues that comprised a death domain, a ProST region, a serine-threonine-specific protein kinase catalytic domain and a C-terminal domain. The amino-acid sequence of C. carpio Irak1 protein shared sequence homology with grass carp Ctenopharyngodon idellus (84.5%). The phylogenetic tree of IRAKs separated the polypeptides into four clades, comprising IRAK1s, IRAK2s, IRAK3s and IRAK4s. Cyprinus carpio Irak1 fell into the cluster with previously reported IRAK1s including teleost Irak1s. The irak1 gene was highly expressed in gills, followed by brain, skin, hindgut, buccal epithelium, spleen, foregut, head kidney and liver, and was expressed at lowest levels in gonad and muscle. The irak1 messenger (m)RNA expression was up-regulated in liver, spleen, head kidney, foregut, hindgut, gills and skin after stimulation with Vibrio anguillarum and poly(I:C), and significantly high up-regulated expression was observed in liver and spleen. These results implied that irak1 might participate in antibacterial and antiviral innate immunity. These findings gave the indications that irak1 may participate in antibacterial and antiviral immunity., (© 2015 The Fisheries Society of the British Isles.)

Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients., (© 2015 British Society for Immunology.)

Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue (NA) therapy and the impact of these changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and cccDNA via real-time fluorescent PCR. In situ detection of CD4(+) , CD8(+) T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV-specific IFN-γ-producing CD4(+) T cells in patients with HBeAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8(+) T lymphocytes increased in patients with HBeAg loss compared with baseline values. Only one patient without HBeAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV-DNA decline, which could promote the recovery of antiviral immunity and facilitate HBeAg loss., (© 2014 John Wiley & Sons Ltd.)