Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Surveillance of avian influenza viruses in live bird markets of Shandong province from 2013 to 2019.

Avian influenza viruses (AIVs) seriously affect the poultry industry and pose a great threat to humans. Timely surveillance of AIVs is the basis for preparedness of the virus. This study reported the long-term surveillance of AIVs in the live bird market (LBM) of 16 cities in Shandong province from 2013 to 2019. A total of 29,895 samples were obtained and the overall positive rate of AIVs was 9.7%. The H9 was found to be the most predominant subtype in most of the time and contributed most to the monthly positve rate of AIVs as supported by the univariate and multivariate analysis, while H5 and H7 only circulated in some short periods. Then, the whole-genome sequences of 62 representative H9N2 viruses including one human isolate from a 7-year-old boy in were determined and they were genetically similar to each other with the median pairwise sequence identities ranging from 0.96 to 0.98 for all segments. The newly sequenced viruses were most similar to viruses isolated in chickens in mainland China, especially the provinces in Eastern China. Phylogenetic analysis showed that these newly sequenced H9N2 viruses belonged to the same clade for all segments except PB1. Nearly all of these viruses belonged to the G57 genotype which has dominated in China since 2010. Finally, several molecular markers associated with human adaptation, mammalian virulence, and drug resistance were identified in the newly sequenced H9N2 viruses. Overall, the study deepens our understanding of the epidemic and evolution of AIVs and provides a basis for effective control of AIVs in China.

Micronutrient Level Is Negatively Correlated with the Neutrophil-Lymphocyte Ratio in Patients with Severe COVID-19.

Aim: To explore the potential relationship between NLR and micronutrient deficiency in patients with severe COVID-19 infection. Methods: Sixteen patients were categorized into the mild group (mild COVID-19) and severe group (severe COVID-19) based on the guideline of the management of COVID-19. The lactate dehydrogenase (LDH); superoxide dismutase (SOD), the inflammatory markers (neutrophil lymphocyte ratio (NLR)), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), selenium (Se), iron (Fe), zinc (Zn), nickel (Ni), copper (Cu), chromium (Cr), cadmium (Cd), arsenic (As), and manganese (Mn) were measured in the blood. Results: Compared to the mild group, the NLR (P < 0.05) and the level of Se (P < 0.01), Fe (P < 0.05), and Zn (P < 0.05) were significantly decreased in the severe group. The level of Se, Fe, and Zn was significantly correlated to NLR levels. Furthermore, close positive correlation was found between NLR and severity of COVID-19. Conclusion: The micronutrient deficiency in the blood is associated with NLR in the severity of COVID-19 patients.

Incidence, circulation, and spatiotemporal analysis of seasonal influenza in Shandong, China, 2008-2019: A retrospective study.

BACKGROUND: Understanding the influenza-like illness (ILI) incidence, circulation pattern of virus strains and spatiotemporal pattern of influenza transmission are important for designing control interventions. Based on the 10 years' surveillance data, we aimed to provide a baseline characterization and the epidemiology and dynamics of influenza virus in Shandong. METHODS: We extracted surveillance and laboratory testing data. We estimated the ILI incidence and analyzed the predominant virus. A wavelet power analysis was used to illustrate the periodicity. In addition, we applied a linear regression model to characterize the correlation of influenza seasonality with longitude. RESULTS: The average ILI incidence was estimated to be 3744.79 per 1 million (95% confidence interval [CI]: 2558.09-4931.45) during 2009-2018. Influenza A/H1N1 and A/H3N2 strains predominated in the most influenza seasons in Shandong. The annual amplitude of influenza epidemics decreased with longitude (P < 0.05). In contrast, the epidemic peak of influenza emerged earlier in the western region and increased with longitude in influenza A (P < 0.05). The annual peak of the influenza B epidemic lagged a median of 4.2 weeks compared with that of influenza A. CONCLUSIONS: The development or modification of seasonal influenza vaccination strategies requires the recognition that the incidence is higher in preschool- and school-aged children. Although seasonal influenza circulates annually in Shandong, the predominant virus strain circulation pattern is extremely unpredictable and strengthening surveillance for the predominant virus strain is necessary. Lower longitude inland regions need to take nonpharmaceutical or pharmaceutical interventions in advance during influenza high-occurrence seasons.

Effects of ambient temperature on influenza-like illness: A multicity analysis in Shandong Province, China, 2014-2017.

Background: The associations between ambient temperature and influenza-like illness (ILI) have been investigated in previous studies. However, they have inconsistent results. The purpose of this study was to estimate the effect of ambient temperature on ILI in Shandong Province, China. Methods: Weekly ILI surveillance and meteorological data over 2014-2017 of the Shandong Province were collected from the Shandong Center for Disease Control and Prevention and the China Meteorological Data Service Center, respectively. A distributed lag non-linear model was adopted to estimate the city-specific temperature-ILI relationships, which were used to pool the regional-level and provincial-level estimates through a multivariate meta-analysis. Results: There were 911,743 ILI cases reported in the study area between 2014 and 2017. The risk of ILI increased with decreasing weekly ambient temperature at the provincial level, and the effect was statistically significant when the temperature was <-1.5°C (RR = 1.24, 95% CI: 1.00-1.54). We found that the relationship between temperature and ILI showed an L-shaped curve at the regional level, except for Southern Shandong (S-shaped). The risk of ILI was influenced by cold, with significant lags from 2.5 to 3 weeks, and no significant effect of heat on ILI was found. Conclusion: Our findings confirm that low temperatures significantly increased the risk of ILI in the study area. In addition, the cold effect of ambient temperature may cause more risk of ILI than the hot effect. The findings have significant implications for developing strategies to control ILI and respond to climate change.

An epigenome-wide DNA methylation study of patients with COVID-19.

In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different disease severities. We conducted a combined analysis and selected 35 "marker" genes that could indicate a SARS-CoV-2 infection, including 12 (ATHL1, CHN2, CHST15, CPLX2, CRHR2, DCAKD, GNAI2, HECW1, HYAL1, MIR510, PDE11A, and SMG6) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the "Severe versus Mild" group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes (GNG7, GNAS, PRKCZ, and PRKAG2) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non-ignorable role in the progression of COVID-19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID-19 and may provide possibilities for specific treatments.

Imported dengue serotype 1 outbreak in a non-endemic region, China, 2017: A molecular and seroepidemiological study.

OBJECTIVES: Beginning in June 2017, numerous dengue virus (DENV) infections occurred in the Jining City of Shandong Province, formerly a dengue-free region in East China. We sought to describe the clinical and epidemiological features of this outbreak. METHODS: We reviewed the clinical records and epidemiological data regarding a case series of patients diagnosed with DENV in Jining City, from June 30 to September 14, 2017. Diagnosis was confirmed by molecular method, culture, or rapid diagnostic tests. Sequencing of the DENV envelope gene or the whole viral genome was performed for 11 patients. Additionally, neutralizing antibodies against DENV was measured among patients and residents from their same villages. RESULTS: Data from 150 patients were evaluated in this outbreak. None were diagnosed with dengue hemorrhagic fever or dengue shock syndrome. The patients' ages ranged between 2-88 years (median 51 years, [IQR=37.5-64.3]), and 100 (66.7%) were female. Epidemiological analyses implicated a man who had visited Saudi Arabia as the likely source of the outbreak. Phylogenetic studies identified DENV serotype 1. Most of the patients demonstrated increases of neutralizing antibody titers one year after infection compared with titers three months after infection. The residents living in dengue-affected villages had a significant higher seroprevalence of 21.2% (95%CI 16.9-25.5) than residents (3.2%, 95%CI-0.36-6.7) living in a non-dengue-affected village. CONCLUSIONS: This report documents the first dengue outbreak in Shandong Province, China, in more than 60 years. It underscores the need for medical providers to record patients' travel histories and to consider dengue in their differential diagnoses.

The Analysis of Gene Expression on Fertility Decline in Caenorhabditis elegans after the Treatment with 5-Fluorouracil.

BACKGROUND: 5-Fluorouracil could lead to a decline in fertility in Caenorhabditis elegans. The aim of this study was to describe the mechanisms underlying such an altered fertility phenotype and to illustrate the specific genes and pathways that are involved in the related phenotypic changes in C. elegans. METHODS: We isolated total RNA from the samples and used a new method called Digital Gene Expression (DGE), which can rapidly identify genes with altered transcript levels. The random genes were confirmed by real-time RT-PCR. RESULTS: We analyzed the results of two methods to draw conclusions based on a comparison between C. elegans and other harmful parasites. Compared with controls, 1147 genes were up-regulated, and 1067 were down-regulated. Overall, 101 up-regulated genes had a log2 ratio higher than 8, whereas the log2 ratio of 141 down-regulated genes was higher than 8. After mapping to the reference database, 4 pathways were confirmed to be involved in this phenomenon, with statistically significant participation from 19 genes. CONCLUSION: For the first time, the transcript sequence of 5-Fu-treated worms and controls was detected. We found that 4 possible pathways, i.e., ECM-receptor interaction pathway, TGF-beta signaling pathway, Focal adhesion and Hypertrophic cardiomyopathy, may be involved in the number decline in the embryos of C. elegans. Specifically, the ECM-receptor interaction pathway and Focal adhesion may be very important pathways that alter the reproduction of C. elegans.

[Status of acute upper respiratory infection, influenza-like illness, and influenza vaccination coverage among community residents in Jinan].

OBJECTIVE: To analyze the status of acute upper respiratory infection and influenza-like illness (ILI) among community residents in Jinan in 2015, and to make a understand of the patient's medical treatment behavior and influenza vaccination coverage status in 2014. METHODS: Balloting method and convenient sampling method were used to launch a household survey. The residents who had been in Jinan for more than 3 months were selected, to investigate the residents' attack ratio of acute upper respiratory and influenza-like from Jan. 8 to Feb. 7, 2015. Totally, 1 300 persons from 410 families were involved in this survey which recovered 1 241 valid questionnaires with the efficiency of 95.5%. Based on the national age-urban demographic statistics in 2010, the attack rates of acute respiratory infections, influenza-like illness were estimated by the direct standardization method, and the influenza vaccination rates were also calculated in this study. χ(2)-test method was used to compare the different status of incidence and vaccination among residents with different features. RESULTS: The attack rate of acute upper respiratory infection and influenza-like illness in Jinan from January 8, 2015 to February 7, 2015 were 30.2% (375 cases), and 6.1% (76 cases), respectively, with a standardized rate of 29.1% and 5.4%. 5.3% (66 cases) of the residents have vaccinated with the influenza vaccine inoculation, with an adjusted rate of 3.8%. The attack rate difference of acute upper respiratory tract infections was statistically significant between each age group (χ(2)=17.121, P= 0.002). The 0-4 age group had a highest attack rate (45.4%) of acute respiratory infection, while the 15-24 age group got the lowest (26.5%). 38.9% (146 cases) of patients went for a treatment in hospital. Among them, 37.7% (55 cases) of them selected the county level hospitals for treatment, 37.7% (55 cases) selected the community level hospitals, and 24.6% (36 cases) selected the individual clinic. Significant differences of influenza-like illness attack rate between each age group were also found in this study (χ(2)=76.79, P<0.001). 0-4 age group had the highest attack rate (22.7%). 81.6% (62 cases) of the ILI sought treatment in the hospital, of which 53.2% (33 cases) selected county level hospital or above, and 33.9% (21 cases) selected community hospital, and 12.9% (8 cases) selected the individual clinic. CONCLUSION: The attack rate of acute upper respiratory infections among the residents of Jinan was high, whereas that of influenza-like illness was relatively low. 0-4 age group had a higher risk of ILI than other age groups. Most of the cases were likely to take the treatment in large hospitals. In general, the coverage rate of influenza vaccination was relatively low.

Efficacy and safety of different dosages of praziquantel for the treatment of schistosoma japonicum: a systematic review and meta-analysis.

BACKGROUND: Praziquantel, an antischistosomal compound, is used as first-line drug for chemotherapy of Schistosoma japonicum since 1984. In this article, we conducted a systematic review and mete-analysis to evaluate the efficacy and safety of different dosages of praziquantel (PZQ) for treatment of Schistosoma japonicum. EVIDENCE ACQUISITION: A number of six articles published in peer-reviewed journals before December 2012 were selected for analysis after searching the following literature databases: PubMed/Medline, the Chinese WanFang Literature Database, China National Knowledge Infrastructure (1994-2012.12), and the Chinese Biomedical Literature (1978-2012.12). RESULTS: The meta-analyses showed that there is no statistically significant difference of the negative rate on the egg using 40 mg/kg compared to 60 mg/kg PZQ for S. japonicum treatment (RR 0.79, 95% CI 0.46 1.35; P < 0.39). The meta-analysis showed that there is no statistically significant difference of the side effects using 30 mg/kg compared with 40 mg/kg (RR 0.97, 95% CI 0.68 1.38; P = 0.87), 40 mg/kg compared with 60 mg/kg (RR 0.79, 95% CI 0.46 1.35; P = 0.39) and 50 mg/kg compared with 60 mg/kg (RR 0.89, 95% CI 0.56 1.42; P = 0.63). CONCLUSIONS: According to the results, there is no statistically significant difference in different doses of PZQ for treating S. japonicum.

Efficacy and safety of omega-3 fatty acids for the prevention of atrial fibrillation: a meta-analysis.

BACKGROUND: The effects of omega-3 fatty acids (PUFA) on the prevention of atrial fibrillation (AF) appear to contrast between several randomized controlled trials (RCTs). Therefore, we performed a meta-analysis to assess the efficacy and safety of PUFA for the primary and secondary prevention of AF. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database were searched for randomized controlled trials (published up to January 2012) that compared PUFA with control. All statistical analyses were performed with RevMan (version 5.1; The Cochrane Collaboration, Oxford, United Kingdom). RESULTS: For primary prevention after open heart surgery: 6 studies with 928 patients were designed to evaluate the effects of PUFA on the incidence of postoperative AF. The use of PUFA significantly reduced the incidence of postoperative AF (odds ratio [OR] 0.66; 95% confidence interval [CI], 0.49 to 0.88; P = 0.004); there was no difference in complications or adverse events (OR, 1.24; 95% CI, 0.58-2.62; P = 0.58). For secondary prevention, we analyzed 5 studies involving 1256 patients designed to evaluate the effects of PUFA therapy on AF. The use of PUFA did not significantly reduce the recurrence of AF (OR, 0.74; 95% CI, 0.39-1.42; P = 0.37); no difference was observed in complications or adverse events (OR, 1.10; 95% CI, 0.78-1.57; P = 0.58). CONCLUSIONS: The meta-analysis shows that PUFA therapy is significantly associated with a decreased odds of incidence of AF after open heart surgery, but there is no significant difference in recurrence of AF between PUFA and control groups. PUFA is well-tolerated, with no difference in complications or adverse events between PUFA and control groups.

[The cellular and molecular mechanism of inhibitory effect of asiaticoside on capsular contracture following breast augmentation].

OBJECTIVE: To explore the cellular and molecular mechanism of the inhibitory effect of asiaticoside on capsular contracture following breast augmentation. METHODS: Contracture capsule derived fibroblasts were cultured in medium with different concentration of asiaticoside. The cell proliferation, collage synthesis and alpha-SMA expression were detected by means of 3H-thymidine incorporation, 3H-proline incorporation, and Western-blot. The results were analyzed by SPSS 11.0 with t test. RESULTS: DNA and collagen synthesis of fibroblasts were dramatically inhibited when the asiaticoside reached the concentration of 50 mg/L. The inhibitory rate was 34.7% and 30.1% respectively, showing a significant difference from that in control group (P < 0.05). The inhibitory effect increased with the rise of the asiaticoside concentration in a dose-dependent manner. When the concentration of asiaticoside reached 25 mg/L, the expression of alpha-SMA was down-regulated with an activation index of 1.673, showing a significant difference when compared with that in control group (P < 0.05). CONCLUSIONS: asiaticoside can effectively inhibit the DNA and collagen synthesis of capsule-derived fibroblasts. The trans-differentiation of fibroblast to myo-fibroblasts is also prevented by it.

[Significance of the secreted frizzled-related protein 2 expression in earlobe keloid].

OBJECTIVE: To investigate the expression and the role of secreted frizzled-related protein 2 (SFRP2) in the earlobe keloid and find a valid way to treat the keloid with gene therapy. METHODS: The expression of SFRP2 mRNA and protein was tested with in situ hybridization and Western Blot Analysis method in the different period of earlobe keloid. RESULTS: The SFRP2 mRNA and protein expression at the keloid edge was significantly high in 12 month group than in 3 or 6 month groups (P < 0.01), but not than in 24 month group. The SFRP2 expression started to decrease in the keloid center 12 month later (P < 0.01). The SFRP2 expression was always higher in edge than in center during all the period (P < 0.05, P < 0.01). CONCLUSIONS: The results suggest that SFRP2 may play an important role in the development of keloid, especially at the keloid edge. The high SFRP2 expression in endothelial cells and surrounding tissue is also important. It may be a new way for gene therapy of keloid by decreasing the SFRP2 expression.

Clinical application of scrotal flap on penis lengthening.

OBJECTIVE: To investigate the clinical application of the scrotal flap on penis lengthening. METHODS: One hundred and fifty-two patients were operated using the scrotal flap from July 1998 to January 2008 at the Department of Plastic and Aesthetic, Surgery Southwest Hospital, Chongqing, China. The procedure consisted of designing a positive sign shaped incision 1.5cm above the root of the penis, dissect and release the superficial suspensory ligament and part of the deep suspensory ligament, then cover the elongated cavernosum with proper scrotal flap. RESULTS: Six-month to 5-year follow-up showed that all patients were satisfied with the good contour and function of the penis. The operation was successful. CONCLUSION: The method of using scrotal flap on penis lengthening has the following advantages: simple operation, reliable blood supply of the flap, one-stage operation, and satisfactory postoperative results. It is a preferable operation technique for penis lengthening.

[Analysis of the adult penis 3D digitized image].

OBJECTIVE: To analyze 3D digitized image of the adult penis, providing morphological data for plastic plerosis of the adult penis diagnosis and the surgery planning. METHODS: 200 adult penis were measured at the length and perimeter of the resting state and erection, and the relation among the erectile angle and length, perimeter were analyzed by the Angel Digital Image Studio software. RESULTS: Penis increase with the age and stature growing. But the length increases in not the same ratio with the stature . With the erectile angle increasing, penile hardness is becoming strong, but penile volume do not marked change. CONCLUSIONS: The digitized model of the penis and adjacent structure offer unique insights into the complex penis anatomy, providing morphological data for preoperative design and postoperative effective evaluation of the penile plastic plerosis.

[Influence of substance P on the release of histamine in the human hypertrophic scar tissue].

OBJECTIVE: To investigate the influence of substance P (SP) on the release of histamine in the human hypertrophic scar tissue, and to explore the prerequisite of their interaction. METHODS: Tissue specimens of normal skin and hypertrophic scar from eight hospitalized patients were excised and cut into 0.5 to 1.0 mm3 pieces, and the histamine release by mast cell (MC) under the stimulation of different concentration of SP and calcium, as well as the different affect time of SP, were determined with fluorescence spectrometer. Then the histamine release rate was calculated. RESULTS: There was obvious release of histamine when SP concentration was 1 x 10(-6) mol/L , and the release rate was (50.0 +/- 3.6) %, which was significantly higher than that by SP in the concentration of 0 mol/L [(44.0 +/- 3.2) %, P < 0.01]. Therefore it seemed to be dose-dependent. About 90% of histamine was released within 15 minutes of 5 x 10(-1) mol/L Substance P stimulation, and it was also time-dependent. The histamine release reached the peak when calcium concentration was 5 x 10(-3) mol/L, which seemed to be dose-dependent, but it decreased transiently when calcium concentration was 1 x 10(-3) mol/L. In all occasions, the influence of SP on the histamine release by MC in hypertrophic scar (HS) was markedly higher than that in normal skin (NS) (P < 0.01). Conclusion The influence of SP on the histamine release by MC in HS was markedly higher than that in NS, and it might be closely related to itching sensation and the formation of hypertrophic scar.

[Establishment of an animal model of human hyperplastic scar in nude mice].

OBJECTIVE: To establish an ideal model of human hyperplastic scar (HS) in nude mice, so as to provide us a new model to carry out further studies on the mechanism of HS development. METHODS: Full skin defect sized 2.0 cm x 1.5 cm was created on the back of 100 nude mice. The defect was thereafter covered with full thickness human skin. After the grafted skin survived, the nude mice were subjected to deep partial thickness burn of the grafted skin with heated copper rod. The development of the hyperplasia of the scar after wound healing was observed histologically and grossly. RESULTS: Grafted full-thickness human skin took and survived well in 86 out of 100 nude mice. There was obvious and continuous hyperplasia of scar in 67 mice (78%). The external appearance and histological features of the HS appeared similar to those in human HS. The average thickness of the scar was 0.34 cm, with the thickest part measuring 0.6 cm. In addition, the time of hyperplastic change lasted for 63 - 217 days in average of 128 days. CONCLUSION: Obvious and continuous scar hyperplasia could be found in this model, and the whole process beginning from wound healing to the formation of HS could be easily observed. The model was therefore suitable and ideal for the study of HS.