Antiviral therapy is the basic treatment method for improving prognosis recommended in the management guidelines of chronic hepatitis B in China and globally. For patients with chronic HBV infection and normal transaminases, it is difficult in clinical practice to accurately evaluate the progression of hepatitis and identify suitable patients who need antiviral therapy. In order to objectively and accurately evaluate the degree of liver inflammatory activity in such patients, more and more noninvasive evaluation indicators have been used in addition to conventional liver biopsy. This article reviews the new serological indicators that can reflect the degree of liver inflammation and/or fibrosis in patients with chronic HBV infection and normal aminotransferase levels, hoping to provide a reference for antiviral decision-making in these patients.

Objective:To evaluate the effect of synthetic CpG oligodeoxynucleotide (CpG-ODN) as adjuvant on immune response induced by inactivated human adenovirus (HAdV)-55 antigen in BALB/c mice.Methods:HAdV-55 virus QS prototype strain was purified by plaque to construct a seed bank of vaccine candidate strain. The amplified product of vaccine candidate strain was inactivated by 0.05%β-propiolactone, and purified to prepare perfect virus particle antigen. The purified HAdV-55 antigen was mixed with the same volume CPG-ODN and aluminum hydroxide adjuvant in low-dose group (0.2 mg/ml) and high-dose group (1 mg/ml), respectively, and inoculated BALB/c mice after emulsification. Meanwhile, the control group was set with PBS, and the immunization was enhanced once every 21 days. Respectively on primary immune 21 and 35 days after collecting venous blood in mice and separation of serum, serum was collected at the end of the time of separating spleen lymphocytes in mice. The levels of HAdV-55 specific IgG antibody and neutralization antibody in serum of immunized mice were observed by ELISA and micro-neutralization test, and the levels of lymphocytes secreting IL-4 and IFN-γ cytokines were detected by ELISpot.Results:No matter with or without adjuvant, along with the increase of the number of immunization and vaccination dose of inactivated HAdV-55 antigen induced BALB/c mice virus specific IgG antibody was also significantly increased. However, neutralizing antibody can reach detectable level only after enhanced immunity, and the geometric mean titer (GMT) of neutralizing antibody is between 1: 11 and 1: 23. Different adjuvants have significant effects on the immune response of mice. Low dose antigen combined with CPG-ODN and aluminum hydroxide mixed adjuvant can induce higher humoral and cellular immune responses in mice, and the levels of specific IgG antibody and neutralizing antibody are 2.2 and 1.8 times higher than those in the aluminum hydroxide adjuvant group, respectively. The number of lymphocytes secreting IFN-γ was 2.3 times that of the group immunized with aluminum hydroxide adjuvant.Conclusions:The novel CPG-ODN adjuvant significantly increased the immunogenicity of the inactivated HAdV-55 whole virus antigen in BALB/c mice and directed the cellular immune response toward Th1 type.

Objective To investigate the expression of malondialdehyde ( MDA) in esophageal mu-cosa of different types of gastroesophageal reflux disease ( GERD) patients and its role in the esophageal in-flammation. Methods According to the inclusion and exclusion criteria, 42 patients hospitalized in the the Xinjiang Uygur Autonomous Region People's Hospital from December 2017 to October 2018 were selected as the research group. 8 healthy subjects completed physical examination were set up as healthy control group. GERD completed GERDQ score, 24 h pH monitoring, and taken 3 cm on the dentate line of the esophagus as a specimen. The study group was divided into non-erosive reflux disease (NERD) group (17 cases) and Ero-sive reflux disease [erosive esophagitis (RE)] group (25 cases). Then hematoxylin-eosin (HE) staining, immunohistochemistry, real-time polymerase chain reaction ( qPCR ) , enzyme-linked immunosorbent assay (ELISA) methods were used to detect inflammation, oxidative stress (MDA), antioxidant enzyme [manga-nese superoxide dismutase (Mn SOD), glutathione (GSH), catalase (CAT)], and proinflammatory cyto-kines [monocyte chemotactic protein-1 (MCP-1), interlukin-8 (IL-8), tumor necrosis factorα(TNF-α)]. Results There was no significant difference in body mass index ( BMI ) between the three groups ( P >0. 05). 24 h pH monitoring of esophagus showed that the indexes of weak acid reflux (40. 05). In RE group , the infiltration of immune cells (neutrophils, eosinophils), nipple lengthening, edema and other inflammatory changes were found in the esophageal mucosa, and the inflammation score reached the peak, which was signif-icantly higher than that in NERD group, with statistical significant difference (P<0. 001). The positive ex-pression of MDA in the two groups ( NERD, RE) was higher than that in the control group, and the MDA ex-pression in the RE group was almost covered with the full layer esophagus. The serum MDA concentration in the NERD and RE groups was significantly higher than that in the control group (P<0. 001). Compared with the NERD group, the serum MDA in the RE group reached the peak (P<0. 01). The relative expression of mRNA ( Mn SOD, GSH and CAT) in NERD group and RE group was significantly decreased, and there was a significant difference between the three groups (P<0. 001). Compared with the NERD group, the mRNA expression level of Mn SOD and CAT in RE group was significantly decreased (P<0. 01). The relative ex-pression of mRNA (MCP-1, IL-8, TNF- α) increased significantly in the two groups (NERD, RE), and there was a statistically significant difference between the three groups ( P <0. 001 ) . Compared with the NERD group, the expression of its inflammatory factors in the RE group significantly increased (P<0. 01). Conclusions The expression level of MDA in different types of GERD is significantly higher, which may be closely related to esophageal inflammation induced by acid reflux.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Objective The aims of this study were to construct short hairpin RNA(shRNA)lentiviral vector in breast cancer T47D cells,to carry out RNA interference on lysine acetyltransferase 6B(KAT6B/MORF)gene,to down-regulate its expression and to explore its function.Methods Two pairs of single-stranded short hairpin RNA(shRNA5 and shRNA8)and the corresponding control sequences(Scramble5 and Scramble8)were synthesized based on the CDS of KAT6B gene.Polymerase chain reaction(PCR) was used to amplify double-stranded and ligated with the entry vector(pENTR/pSM2(CMV)GFP),which were subjected to a doub-le digestion(EcoRl and Xhol)linearization and homologous recombination with the entry vector(pENTR/pSM2(CMV)GFP)to obtain an entry clone containing the desired fragment.The target fragment was recombined onto the target vector(pLenti x1 puro DEST)via the LR cloning reaction of the Gateway system.The lentiviral packaging plasmids were co-transfected into HEK-293T cells with two pairs of target plasmids. The supernatant of HEK -293T cells was collected and transformed into T47D cells. The expression of KAT6B protein was detected in T47D cells by Western blot.Results The single colony obtained from the transformation was identi-fied by sequencing,which was consistent with the target sequence,indicating that the lentiviral vector had been successfully construc-ted.The expression of KAT6B protein was significantly lower in the shRNA KAT6B group than that in the control group,which indica-ted that the constructed gene silencing vector could play a role in the KAT6B gene in T47D cells.Conclusion The shRNA lentiviral gene silencing vectors of KAT6B were constructed and identified in T47D cells,which indicated that the foundation for further study

Objective To analyze the amount and allocation of pediatric healthcare resources in Chengdu,and to recommend on local pediatric healthcare resources shortages.Methods Pediatric healthcare resources data of Chengdu came from pediatric relevant data reported regularly at yearend by the counties and districts to healthcare administration of the city.Data from such reports were subject to statistics with various indexes and descriptive analysis.Analyzed in focus was the distribution in 2015 of pediatric healthcare resources of the city among medical institutions of various types,levels and properties,as well as causes for such shortage.Results Tertiary hospitals hold 62.3% of the pediatric beds and 64.2% of pediatricians,and provide around 70% of the medical workload for pediatric outpatients and inpatients,upon the majority of pediatricians with master degree and above,and senior ones of/above associate chief physician titles;Tertiary hospitals have 58.7% of the pediatric beds and 49.7% of pediatricians,yet the outpatients served by specialized hospitals were 5% above tertiary hospitals.Conclusions The imbalance and shortage in total of pediatric resources in Chengdu result from stable source of manpower supply,high professional risk exposure,low income,and long training duration among others.Such measures as a better pediatrician development system,greater incentives for pediatric development,and enhanced development pediatric service consortiums,as well as greater support for private specialized pediatric hospitals.Those measures combined can effectively alleviate the shortage of pediatric resources.

OBJECTIVETo analyze the results of pathogenic bacteria culture on chronic periprosthetic joint infection after total knee arthroplasty (TKA) and total hip arthroplasty (THA).

METHODSThe medical data of 23 patients with chronic periprosthetic joint infection after TKA or THA from September 2010 to March 2014 were reviewed. Fifteen cases of TKA and 8 cases of THA were included in this study. There were 12 male and 11 female patients with the mean age of 62 years (range from 32 to 79 years), and among them 9 patients with sinus. All patients discontinued antibiotic therapy for a minimum of 2 weeks before arthrocentesis, taking pathogenic bacteria culture and antimicrobial susceptibility test by using synovial fluid taken preoperatively and intraoperatively of revision. Common pathogenic bacteria culture and pathological biopsy were taken on tissues intraoperatively of revision. Culture-negative specimens were prolonged the period of incubation for 2 weeks.

RESULTSThe overall culture-positive rate of all 23 patients for 1 week before revision was 30.4% (7/23), and the positive rate of culture-negative samples which prolonged for 2 weeks was 39.1% (9/23). The overall culture-positive rate of patients for 1 week intraoperatively of revision was 60.9% (14/23), and the positive rate of culture-negative samples which prolonged for 2 weeks was 82.6% (19/23). The incubation results of 7 cases (30.4%) preoperatively conformed to that of intraoperation.

CONCLUSIONThe culture-positive rate of pathogenic bacteria culture can be increased evidently by discontinuing antimicrobial therapy for a minimum of 2 weeks prior to the definite diagnosis.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Bacteria ; isolation & purification ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Prosthesis-Related Infections ; Reoperation

OBJECTIVETo investigate the feasibility,safety and follow-up results of multiple stents parallel placement and reconstruction technique for treating giant vertebrobasilar dissecting aneurysms.

METHODSFive consecutive patients with giant fusiform vertebrobasilar dissecting aneurysms in Department of Neurology,Chinese People's Liberation Army General Hospital were retrospectively reviewed from April 2011 to October 2013. All patients were diagnosed vertebrobasilar dissecting aneurysms by MRI and digital subtraction angiography (DSA), the aneurysm size ranged 8.2-15.0 mm. All patients were treated by multiple stents parallel placement and reconstruction technique under general anesthesia. In the endovascular treatment process, 2-3 Solitaire or Neuroform self-expandable stents were parallel implanted in the maximum extension segment of the aneurysms to reconstruct the cavity of the aneurysm and solved the problem that the diameter of the intracranial stent is less than the diameter of the aneurysms. Multiple stents parallel placement can keep the stents stable in the cavity. The parallel stent can close the dissection as well as strengthen the aneurysm walls to alleviate the vessel pulsative compression of the brain stem. Furthermore, one of the parallel stents was selected for the main blood flow channel. Based on the main channel, telescope technique was used to completely covering the dissection. It can not only prevent the progress of dissection to normal regions, but also be helpful for blood flow channel reconstruction to reduce the hemodynamic disorders. All Patients received routine antiplatelet therapy before and after endovascular treatment.

RESULTSThe operative procedures were succeeded in all patients. Five patients were implanted 18 stents (3 stents in 3 patients; 4 stents in 1 patient; 5 stents in 1 patient; parallel 3 stents in 2 patients; parallel 2 stents in 3 patients). The signs and symptoms of brain stem and posterior group of cranial nerves improved significantly. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6-24 months. All patients performed DSA reexamination at 6-12 months postoperation. The aneurysm size lessened in 2 patients and had no change in 3 patients.

CONCLUSIONSMultiple stents parallel placement and reconstruction technique for treating giant fusiform vertebrobasilar dissecting aneurysms is feasible and have good operation safety. It may control the dilatation of the aneurysm and reduce the probability of thrombosis or hemorrhage. It can improve the patients' clinical symptoms and quality of life in short term follow-up. The long term result need for further follow-up.

Aneurysm, Dissecting ; surgery ; Humans ; Intracranial Aneurysm ; surgery ; Quality of Life ; Retrospective Studies ; Stents ; Treatment Outcome

Objective To investigate the expression level and clinical significance of WT1 gene in acute luekemia (AL) patients.Methods WT1 gene level was detected by real time quantitative-polymerase chain reaction in acute myelogenous leukemia (AML) and in acute lymphocytic leukemia (ALL) patients.Then the expression levels of WT1 gene in different subtypes of AML were compared,and the correlation between gene expression and disease courses and prognosis were observed.Moreover,the relationship between disease courses and WT1 expression in patiens after receiving haemopoietic stem cell transplantation were analyzed.Results Among 66 cases,WT1 expression positive rate was 87.5 ％ (14/16) in AML and 76.0 ％ (38/50) in ALL.In AML,the expression level in M3 showed the lowest than that in any other subtypes (compared with M1,M2,M4,M5,P value was 0.040,0.007,0.006 and 0.01,respectively).The expression level of WT1 was closely correlated with leukemia disease courses.The expression level in complete remission (CR) group showed a significant lower expression level than that in non-remission group (P =0.018) and relapse group (P =0.003),and the re-increase of WT1 expression level could predict relapse as early as 1.5 months.Moreover,WT1 expression also showed an close relationship with prognosis of patients receiving haemopoietic stem cell transplantation.Patients whose WT1 was undetectable had a better prognosis than those with persistent expression,and increase again after becoming undetectable.Conclusion WT1 has a high expression level in AL,which can represent minimal residual disease.The expression level in M3 was lowest than that in different AML subtypes,and its expression level has a close correlation with clinical disease course and prognosis of AL.

[Objective]To discuss the clinical effect of fludarabine and busulfan (Bu+Flu) as a low toxicity myeloablative conditioning regimen for allogeneic peripheral blood stem cell transplantation (allo-HSCT)in leukemia patients.[Methods]Clinical data of 13 patients with hematological malignancies receiving conditioning regimen with Bu+Flu for allo-HSCT were analyzed retrospectively.Conditioning regimen was Bu+Flu,compalriot mismatched and unrelated transplantation combined with rabbit anti-human thymocytes immune globulin (ATG).CsA+short course of methotrexate or CsA + mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).DNA sequencing of short tandem repeat (STR)polymorphism analysis method was performed for identification of donor stem cells implantation.[Results]13 patients all tolerated with this conditioning regimen well,no serious complications occurred.Neutrophil engraftment was at 9-15 days (median 11 days),platelet engraftment at 8-25 days (median 13 days).10 patients achieved hematopoiesis reconstitution with their full donor chimerisms confirmed by STR-DNA analysis.Acute GVHD occurred in 5 cases,accounting for 38.5％.Chronic GVHD occurred in 4 cases of 10 patients could be assessed,accounting for 40.0％.Severe GVHD more than Ⅱ degree did not happen.1-39 months (median time 11 months)of follow-up revealed the overall survival rate of 76.9％(10/13),disease-free survival of 61.5％ (8/13).The causes for death were relapse in all.[Conclusion]The conditioning regimen with Bu+Flu has low toxicity,well tolerance and better effect.