To explore the effect of apurinic-apyrimidinic endonuclease I (APE-1) on hepatocyte immune inflammatory factors and cell apoptosis. The gene expression profiles of peripheral blood of patients with or without immune tolerance after liver transplantation were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes were analyzed with a program in the R language, and the APE-1 gene was identified as a gene related to immune tolerance of liver transplantation. Four APE-1 shRNA vectors were constructed in parallel and verified as correct using plasmid sequencing, real-time PCR, and Western blotting. An APE-1 overexpression vector was similarly constructed and verified as correct. The STRING website predicted the protein-protein interaction network of APE-1. ELISA was used to detect the effects of APE-1 silencing and overexpression on inflammatory cytokines IL-1β, IL-10, TNFα, and INF-γ in the control group, APE-1-silenced group, and APE-1 overexpression group. Flow cytometry was used to detect apoptosis in each group. Forty differentially expressed genes related to immune tolerance after liver transplantation were screened, and the highly expressed gene APE-1 was selected. The best APE-1 shRNA_1 vector and APE-1 overexpression vector were obtained. APE-1 is predicted to interact with ANP32A, FEN1, HMGB2, LIG1, MUTYH, NTHL1, OGG1, PCNA, POLB, SET, and other proteins. APE-1 silencing resulted in a significant increase in the expression of the inflammatory factors IL-1β, IL-10, TNFα, and INF-γin L-02 cells. In contrast, the expression of APE-1 led to a significant decrease in the expression of inflammatory factors. APE-1 silencing significantly increased the rate of apoptosis of L-02 cells, and APE-1 overexpression resulted in a significant decrease in the rate of apoptosis of L-02 cells. In conclusion APE-1 affects the expression of inflammatory factors and apoptosis in L-02 cells, so it may be a key gene in immune tolerance of liver transplantation.

Bacillus cereus (B. cereus) and Staphylococcus aureus (S. aureus) are major human food-borne pathogens that may produce a variety of toxins and cause diarrhea, food poisoning, and even death. In order to monitor and prevent the spread of these pathogens, a multiplex loop-mediated isothermal amplification (multi-LAMP) assay was developed to simultaneously and rapidly detect B. cereus and S. aureus. The sensitivity and specificity of the loop-mediated isothermal amplification (LAMP) reactions were determined via electrophoresis. The multi-LAMP showed 100% inclusivity and exclusivity, the sensitivity was 10 fg/μL and was 10 times more sensitive than that of polymerase chain reaction (PCR), the results were consistent with those of conventional PCR assay, and the entire assay should be finished within 40 min. This multi-LAMP assay was confirmed as a rapid and reliable diagnostic technique upon application for clinical samples and food samples. To our knowledge, this is the first study to report the application of multi-LAMP to detect B. cereus and S. aureus.

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.5582/bst.2019.01111) revealed a higher, not lower, level of ꞵ-human chorionic gonadotropin (hCG) and estrogen during the first 6 weeks of pregnancy, suggesting a novel association between ꞵ-hCG, estrogen, and threatened abortion. Unfortunately, this study was limited by its small sample size, unconvincing trial design, and inadequate exploration of the underlying mechanisms. This low-quality evidence indicates that a higher level of ꞵ- hCG and estrogen is associated with threatened abortion. However, that work provided some new insights for further studies of threatened abortion.

We construct and validate a non-invasive clinical scoring model to predict mortality in HIV/TB patients at end stage of AIDS in China. There were 1,007 HIV/TB patients admitted to Beijing Ditan Hospital from August 2009 to January 2018 included in this study, who were randomly assigned to form derivation cohort and validation cohort. A clinical scoring model was developed based on predictors associated with mortality identified with Cox proportional hazard models. The discrimination and accuracy of model were further validated using the area under the ROC curves. The derivation and validation cohort consisted of 807 and 200 patients in 8:2 ratio, respectively. In derivation cohort, anemia (HGB < 90g/L), tuberculous meningitis, severe pneumonia, hypoalbuminemia, unexplained infections or space-occupying lesions, and malignancies remained independent risk factors of mortality in HIV/TB co-infected patients, and included in this clinical scoring model. The model indicated good discrimination, including AUC = 0.858 (95% CI: 0.782-0.943) in the derivation cohort, and AUC = 0.867 (95% CI: 0.832-0.902) in validation cohort, respectively. The predicted scores were categorized into two groups to predict the mortality: low-risk (0-2 points with mortality with 3.6-9.1%) and high-risk (4-16 points with mortality with 26.42-74.62%), in which 54.55% and 74.62% of patients with score of 5 to 11 and 12-16 were died among high-risk group. Kaplan-Meier curve indicated a significant difference in the cumulative mortality in the two groups by log-rank test (p < 0.001). A clinical scoring model to assess the prognosis in HIV/TB patients at end stage of AIDS was constructed based on simple laboratory and clinical features available at admission, which may be an easy-to-use tool for physicians to evaluate the prognosis and treatment outcome in HIV/TB co-infected patients. The model was also applicable for predicting the death of end-stage HIV/TB patients within a 12 months period after discharge.

Single nucleotide polymorphisms (SNP) influence the outcome of antiviral therapy in chronic hepatitis B patients. Interferon β promoter stimulator 1 polymorphisms (IPS-1) regulate interferon (IFN) mediated viral clearance in hepatitis B virus (HBV) infection. In our study, HepG2 and HepG2.2.15 were transfected with different SNP genotype expression vectors of IPS-1 (wild-type, rs17857295, rs7262903 and rs7269320). The production of IPS-1 and IFN were evaluated in these transfected cells. IPS-1 in the HepG2.2.15 cells transfected with rs17857295 or rs7262903 was 37% or 31% lower than that with wild-type transfection (p < 0.001). IFN-β in rs17857295 or rs7262903 transfected HepG2.2.15 cells was 5.4 or 3.7 fold higher than that of wild-type transfection (p < 0.0001). IPS-1 in rs7269320 SNP transfected HepG2.2.15 cells was 40% lower than that of wild-type transfection (p < 0.0001); no significantly different IFN-β was observed between rs7269320 SNP and wild-type transfections. IFN-β expression was > 2 fold higher in rs17857295 transfected HepG2.2.15 cells than HepG2 cells (p < 0.001). The data suggests that host HBV viral clearance is stronger in IPS-1 rs17857295 or rs7262903 SNP genotype patients than wild-type patients. Relatively weak inducible IFN-β production in HBV infected patients with IPS-1 rs7269320 SNP or wild-type may contribute to chronic virus infection.

Surgical treatment for intra-abdominal/retroperitoneal desmoid-type fibromatosis (IA/RPDF) is still controversial. Studies regarding en bloc resection in IA/RPDF with adjacent organ involvement are scanty. This study aims to evaluate the safety and effectiveness of en bloc resection in IA/RPDF with adjacent organ involvement. This retrospective clinical study included 21 patients who were diagnosed with IA/RPDF and underwent tumor resection at a single center between March 2013 and June 2018. All patients included in the study underwent surgery with curative intent, and IA/RPDF with adhesive organs was removed en bloc. The safety of surgical treatment was verified by the analysis of intraoperative bleeding, postoperative morbidity and perioperative mortality. The efficacy of surgical treatment was evaluated based on the status of tumor infiltration of adjacent organs and patient follow-up results. Complete macroscopic (R0 or R1) resection was achieved in all cases. A median of 2 (range, 1-7) organs were resected. The median operating time was 300 (90-650) minutes. The median intraoperative bleeding was 300 (20-4,500) milliliters. For postoperative pathological diagnosis at our center, tumor infiltrated at least one organ in each patient. Infiltration was noted in 45 resected organs (45/57, 78.9%). Grade III-V postoperative morbidity developed in one patient (4.8%). During the follow-up, one patient developed local recurrence. No DF-related death was noted during the follow-up. The 3-year disease-free survival rate was 94.1% (95% confidence interval: 83.6-100%). Therefore, en bloc resection of the tumor and involved adjacent organs is a safe and effective treatment modality for IA/RPDF.

In Japan, national official surveillance for influenza has been performed at about 5,000 sentinel hospitals/clinics by the National Official Sentinel Surveillance of Infectious Diseases (NOSSID). Meanwhile, all electronic medical claims nationwide in the National Database of Electronic Medical Claims (NDBEMC) were recently disclosed by the Ministry of Health, Labour and Welfare of Japan. We compared the regional variation of influenza incidence among prefectures between the NOSSID and NDBEMC. The data were extracted from NOSSID and the NDBEMC for the 2010/2011 through 2013/2014 seasons. We compared the data of both datasets season by season by using Spearman's rank correlation in each season. Spearman's rank correlation values for the four seasons were 0.7823, 0.3907, 0.4961 and 0.4543, and their p-values were less than 0.00005, 0.0066, 0.0004 and 0.0013, respectively. Statistically, regional variation of influenza incidence in NOSSID is not imprecise, but its correlation with the NDBEMC dataset is not so high. It is important to note this fact when interpreting regional variation in NOSSID.

Since serious problematic cases regarding the technical safety of technically demanding operations were reported in Japan, the Ministry of Health, Labor and Welfare issued new regulations on June 10, 2016 requiring each hospital to check the status of informed consent, skill of surgery team and governance system of the surgical unit, when the highly difficult new medical technologies were introduced to a hospital. In order to firmly establish this new system for highly difficult new medical technologies, it is very important and informative to survey the current situation for guidelines and consensus regarding introduction of medical technology with special skills in Japan and overseas. Based on the survey of questionnaires, document retrieval, and expert interviews, we found that documentation related to the introduction process of highly difficult medical technologies is very rare, and the regulations were mainly issued by academic societies. Moreover, even if such documentation existed, the quality of the regulations is poor and not sufficient enough to perform surgical practice safely. Therefore, for medical practitioners, comprehensive and concrete regulations should be issued by the government or ministry to legally follow in regard to technically demanding operations. A new practice guideline was proposed by our special research group to regulate the introduction process of highly difficult new medical technologies in hospitals in Japan. This guideline, gained understanding from relevant academic societies, provided a comprehensive view on the interpretation of "high difficulty new medical technology" prescribed by the law and show the basic idea at a preliminary examination from the viewpoints of "Surgeon's requirement", "Guidance system", "Medical safety" , and "Informed consent". These efforts will contribute to the improvement of the quality of guidelines regarding "highly difficult new medical technology".

In order to investigate the genetic causes of hearing loss in a Chinese proband with nonsyndromic hearing loss and enlarged vestibular aqueduct (EVA), we conducted clinical and genetic evaluations in a deaf proband and her parents with normal hearing. 20 exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations by PCR amplification and bidirectional sequencing. As a control, a group of 400 healthy newborns from the same ethnic background were subjected to SLC26A4 gene screening using the same method. The proband harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. She was found to be heterozygous for a novel mutation c.574delC (p.Leu192Ter) in exon 5 and for the known mutation c.919-2A>G(c.IVS7-2A>G). Her mother was a heterozygous carrier of the c.919-2A>G mutation, and her father was a heterozygous carrier of the c.574delC and therefore co-segregated with the genetic disease. The c.574delC mutation was absent in 400 healthy newborns. The frameshift mutation causes the leucine (Leu) at amino acid position 192 to become a termination codon, leading to termination of protein sequence coding. This study demonstrates that the novel frameshift mutation c.574delC (p.Leu192Ter) in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is the main cause of deafness in a family. Our study will expand the spectrum of known SLC26A4 mutations in the Chinese population, providing more information on genetic counseling, and diagnosis in hearing loss with EVA.

Precise diagnosis is a key measurement for malaria control and elimination, traditional microscopy and rapid diagnostic tests cannot satisfy the requirements especially in the low transmission endemic areas or in the malaria elimination phase. Polymerase chain reaction (PCR) with high sensitivity and specificity can be considered as a diagnostic standard while no uniform PCR assay was established due to variations in their performance and lack of formal external quality assurance programs for validation for PCR assays in use. Here, 24 articles including 43 paired comparative evaluations limited to paired comparison of diagnostic performance between real-time PCR and conventional PCR to detect plasmodium in blood samples of human subjects from clinics or the field are systematically summarized. And according to the Landis and Koch classification, nineteen pairs showed almost perfect agreement, followed by 8 pairs of moderate agreement and 4 pairs of good agreement, while the kappa values of 12 pairs couldn't be examined. Moreover, the performance of 14 pairs were completely the same and 8 pairs had no differences, but 14 pairs were significant different including 8 pairs of real-time PCR with better performance than conventional PCR. Therefore, it is still an outstanding issue to choose PCR methods, and more work such as the standardization of materials and methods in use and their availability are needed to settle priority to better promote the role of malaria diagnosis reference laboratories.