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Background To analyze and discuss the transmission route of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). Method We performed an epidemiological investigation and a genetic analysis of patients with severe fever with thrombocytopenia syndrome (SFTS) caused by SFTSV, their close contacts and the surrounding population. Results We found that all patients had contact with the blood of the first patient. The comparison of gene sequences in the three isolated SFTSV strains showed that the strains were closely related. Six close contacts and nine individuals in the surrounding population were positive for SFTSV IgM antibody. Conclusion We suspect that the cluster outbreak was transmitted via blood and that the natural reservoir host of SFTSV exists in the patients’ environment.

Background Vanishing bile duct syndrome (VBDS) is a rare but potentially severe acquired chronic cholestatic liver disease. Bile duct deficiency is a reduction of bile ducts in the liver, which can eventually lead to cholestatic liver disease and progress to biliary cirrhosis. Primary biliary cholangitis (PBC) is one of the causes of bile duct deficiency. In addition, 75% of PBC patients may have dyslipidemia, and in case of secondary dyslipidemia, cutaneous xanthomas may occur. Case summary A 49-year-old woman was admitted with jaundice and multiple subcutaneous nodules. She received diagnosis of autoimmune liver disease 2 years before. Although she was treated with liver-protecting drugs, such as Essentiale and ursodeoxycholic acid, jaundice occurred repeatedly, and the color of her skin was becoming darker and more yellow. Conclusion This case highlights that the positivity of ANA that in PBC have a well diagnostic and prognostic significance and antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim-like/membranous’ pattern scan ca diagnose primary biliary cirrhosis accurately. Since the liver biopsy of PBC alone may not be sufficient to establish the diagnosis, serum antibodies should also be examined. PBC can also lead to intrahepatic cholestasis, which can cause dyslipidemia and cutaneous xanthomas.

Myopia is a major public health concern with increasing global prevalence and is the leading cause of vision loss and complications. The potential role of the cornea, a substantial component of refractive power and the protective fortress of the eye, has been underestimated in the development of myopia. Our study acquired corneal stroma tissues from myopic patients undergoing femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery and investigated the differential expression of circulating proteins between subjects with low and high myopia by means of high-throughput proteomic approaches—the quantitative tandem mass tag (TMT) labeling method and parallel reaction monitoring (PRM) validation. Across all corneal stroma tissue samples, a total of 2,455 proteins were identified qualitatively and quantitatively, 103 of which were differentially expressed between those with low and high myopia. The differentially abundant proteins (DAPs) between the groups of stroma samples mostly demonstrated catalytic activity and molecular function regulator and transporter activity and participated in metabolic processes, biological regulation, response to stimulus, and so forth. Pathway enrichment showed that mineral absorption, ferroptosis, and HIF-1 signaling pathways were activated in the human myopic cornea. Furthermore, TMT analysis and PRM validation revealed that the expression of ferritin light chain (FTL, P02792) and ferritin heavy chain (FTH1, P02794) was negatively associated with myopia development, while the expression of serotransferrin (TF, P02787) was positively related to myopia status. Overall, our results indicated that subjects with low and high myopia could have different proteomic profiles or signatures in the cornea. These findings revealed disturbances in iron metabolism and corneal oxidative stress in the more myopic eyes. Iron metabolic proteins could serve as an essential modulator in the pathogenesis of myopia.

Background We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported . Case presentation A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely. Conclusions The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.

Hepatitis E virus (HEV) infection is a global health concern, with a large number of new infections reported every year. In developing countries with poor sanitation condition, HEV1 and HEV2 are mainly transmitted by the fecal-oral route due to water contamination. HEV3 and HEV4 are zoonotic diseases in humans consuming undercooked pork, mainly in developed countries. Usually, HEV infection is an acute self-limited course, and chronic infection can occur in immunocompromised individuals. The diagnosis of HEV infection relies on sero - logical tests, including RNA and anti-HEV antibodies. Currently, ribavirin is a proven effective drug; the treatment options for immunocompromised and pregnant individuals are limited. To date, only China has approved vaccines for HEV prevention. Therefore, more research is needed to understand the etiology.

Background Severe fever with thrombocytopenia syndrome (SFTS), a novel tick-borne disease caused by SFTS virus (SFTSV), has been reported in China, Japan, South Korea, and Vietnam since 2009. SFTSV infection can cause multiple organ damage, including acute pancreatitis (AP). We summarize the clinical features, treatment and outcome of AP associated with SFTSV. Methods We retrospectively review the clinical manifestations, laboratory tests, treatment, and outcome of AP associated with SFTSV infection from January 2009 to December 2018 in Liaoning Province, China. Results A total of 418 SFTS patients were reviewed. Fifteen (3.6%) of 418 met the criteria for AP associated with SFTSV infection. The first reported symptom for all SFTS-AP patients was fever. All the SFTS-AP patients presented with thrombocytopenia, and 13 (86.7%) of them presented with leukopenia on admission. Thirteen (86.7%) of 15 SFTS-AP patients were severe SFTS patients, and 9 (60.0%) patients were diagnosed with multiple organ dysfunction syndrome. One SFTS-AP patient died of multiple organ failure. Six (40%) of 15 SFTS-AP patients were not confirmed with SFTSV infection when AP was diagnosed, and the median delay between SFTSV infection and AP diagnosis was 5 days (range, 2–7 days). Conclusions AP is not a frequent complication of SFTS, and is more frequently seen in severe SFTS patients. Most patients with SFTS-AP have mild or moderate disease, and can recover with conservative management; however, severe SFTS-AP can be fatal. In SFTS endemic areas, clinicians should be alert to the possibility of SFTS when AP patients with tick exposure, thrombocytopenia, and leukopenia have a fever before abdominal pain.

A 53-year-old male was admitted to the emergency room with 5-day history of fever, bilateral parotid gland swelling, and right esticular pain for 2 days. He also complained of headaches, genralized arthralgias, myalgias, and severe lumbago. He lived in a ural area in Northeast China and had worked in the field 2 weeks rior to the onset of symptoms. He was previously in good health, nd there was no history to suggest a sexually transmitted infecion. He was treated with ibuprofen for 2 days before admission ithout remission of symptoms. The physical examination on admission revealed swelling of the arotid glands bilaterally (Fig. 1) and right scrotum. The vital signs ere as follows: temperature, 37.5 ◦C; heart rate, 80/min; respiatory rate, 20/min; and blood pressure, 120/60 mmHg. Petechiae ere noted in the throat, and the abdomen was soft. Lymhadenopathy was palpable in the neck. There was no conjunctival uffusion, facial suffusion, or cutaneous petechiae. The neurologic xamination was unremarkable. Initial laboratory studies (Table 1) revealed that the leukoyte count was 4890/ L, the hemoglobin level was 12.8 g/dL, the

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently discovered in northeastern and central China that is caused by a novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). Humans are primarily infected through tick bites. Four previous reports have discussed SFTS infection from person to person, all cases of which were symptomatic. In this report, we analysed the epidemiological and clinical data for a cluster of cases, including one case of secondary-asymptomatic infection, and review the literature regarding SFTSV transmission from person to person. We conclude that SFTSV caused the asymptomatic infections via person-to-person contact with infected blood.

Human exposure to inorganic arsenic leads to various dermal disorders, including hyperkeratosis and skin cancer. Curcumin is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at identifying curcumin as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) and demonstrating its protective effect against inorganic arsenite- (iAs3+-) induced cytotoxicity in human keratinocytes. We found that curcumin led to nuclear accumulation of NRF2 protein and increased the expression of antioxidant response element- (ARE-) regulated genes in HaCaT keratinocytes in concentration- and time-dependent manners. High concentration of curcumin (20 μM) also increased protein expression of long isoforms of NRF1. Treatment with low concentrations of curcumin (2.5 or 5 μM) effectively increased the viability and survival of HaCaT cells against iAs3+-induced cytotoxicity as assessed by the MTT assay and flow cytometry and also attenuated iAs3+-induced expression of cleaved caspase-3 and cleaved PARP protein. Selective knockdown ofNRF2orKEAP1by lentiviral shRNAs significantly diminished the cytoprotection conferred by curcumin, suggesting that the protection against iAs3+-induced cytotoxicity is dependent on the activation of NRF2. Our results provided a proof of the concept of using curcumin to activate the NRF2 pathway to alleviate arsenic-induced dermal damage.

Background Although hepatitis B virus (HBV) primarily affects hepatocytes, it has also been shown to cause complications in the skin, joints, muscles, and kidneys. Thyroid dysfunction is uncommon in cases of acute HBV infection. Case presentation In this report, we describe a case of a 46-year-old woman with incipient acute hepatitis B virus (HBV) infection who presented clinically with Graves’ hyperthyroidism. She showed typical symptoms of hyperthyroidism, and laboratory tests revealed high levels of HBV DNA and alanine transaminase (ALT). The patient was not administered with antithyroid medicine or radioiodine, but she was given antiviral therapy and symptomatic treatment with propranolol. Follow-up studies showed that as the HBV DNA levels decreased, the thyroid function recovered. Conclusion Graves’ disease maybe an extrahepatic manifestation of acute HBV infection. Antiviral therapy is likely to be beneficial for this condition as without severe thyrotoxicosis.

Objective The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection. Methods A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software. Results Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case–control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection. Conclusion Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), which can cause hemorrhagic fever-like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups--severe or non-severe--based on disease severity. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin-6, interferon (IFN)-γ, IFN- γ-induced protein (IP)-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.

CBC Leucocytes (n/mm3) 1980 3970–9150 Hemoglobin (g/dL) 17.4 13.1–17.2 Platelets (n/mm3) 30,000 85,000–303,000 CD4 ( L−1) 167 410–1590 CD8 ( L−1) 173 190–1140 CD4/CD8 0.96 0.60–3.20 CRP (mg/L) 7.25 0–8 Biochemical tests Creatine kinase (U/L) >23,000 39–308 Creatine kinase MB fraction (ng/mL) 246 0–7.2 Myoglobin (ng/mL) >1000 0–116 Creatinine ( mol/L) 299 59–104 Blood urea nitrogen (mmol/L) 24.7 3.2–7.1 Na+ (mmol/L) 121.1 136–145 K+ (mmol/L) 8.76 3.5–5.2 Ca2+ (mmol/L) 1.67 2.17–2.57 Alanine aminotransferase (U/L) 179 5–40 Aspartate aminotransferase (U/L) 548 8–40 Lactate dehydrogenase (U/L) 1613 135–225 Troponin I (ng/mL) 0.03 0.00–0.40 Fasting plasma glucose (mmol/L) 26 3.9–6.10 Albumin (g/L) 28.7 40.0–50.0 eceived in revised form 23 June 2012 ccepted 29 June 2012

Background During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics and factors associated with the death of patients who were hospitalized with 2009 H1N1 influenza pneumonia in Shenyang, China, from November to December 2009. Methods We carried out a retrospective chart review of 68 patients who were hospitalized with pneumonia and confirmed to have 2009 H1N1 virus infection by a real time RT-PCR assay of respiratory specimens. Results Of the 68 patients we studied, 30 (44%) were admitted to an intensive care unit and 10 (14.7%) died. The median age of patients was 41 years (range, 18-66), and only one patient was over 65 years of age. The male to female ratio was 2.78:1 (50:18). Of the 68 patients, 23 (34%) had at least one underlying medical condition, 9 (13%) had a cigarette index ≥400 and 22 (32%) were obese. All patients underwent chest radiography on admission and the findings were consistent with pneumonia in all cases. All patients were treated with oseltamivir and treatment was initiated at a median time of seven days after the onset of illness. The laboratory test results indicated lymphopenia, hypoproteinemia and elevated lactic dehydrogenase and C reactive protein levels. Of the 68 patients, 33 (52%) showed a reduction in CD4 T cell counts. Of the 58 patients who survived, 31 (53%) had lymphopenia and 27 recovered from this condition after five days. Of the 10 patients who died, nine (90%) had lymphopenia and only two patients recovered from this condition after five days. Obesity and recovery from lymphopenia after five days were factors associated with death, as determined by multivariate logistic-regression analysis (obesity, odds ratio = 23.06; lymphocytopenia reversion, odds ration = 28.69). Conclusions During the evaluation period in Shenyang, China, 2009 H1N1 influenza caused severe illness requiring hospitalization in 68 patients, 10 (14.7%) of which died. Many of these patients were considered healthy adults and few were elderly (65 years or older). Obesity and lymphopenia, which was not restored after five days of treatment, were factors associated with poor outcomes of 2009 H1N1 influenza infection.