Value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease

Objective:To study the value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease (HFMD). Methods:76 children diagnosed with hand, foot and mouth disease in our hospital between May 2013 and March 2016 were selected as the HFMD group of the research, 80 healthy children receiving physical examination in our hospital during the same period were selected as the control group of the research, and the serum was collected to determine the levels of pattern recognition receptors, immunoglobulins, complements, inflammatory media and target organ damage indexes. Results:Serum Collectin, Dectin and CD14 levels of HFMD group were significantly higher than those of control group (P<0.05);serum immunoglobulin G (IgG) IgM, IgA, C3 and C4 levels of HFMD group were significantly lower than those of control group (P<0.05) and negatively correlated with Collectin, Dectin and CD14 levels;serum PCT, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α(TNF-α), N-terminal pro-brain natriuretic peptide (NT-proBNP), neuron-specific enolase (NSE), S100βand surfactant protein A (SP-A) levels of HFMD group were significantly higher than those of control group (P<0.05) and positively correlated with Collectin, Dectin and CD14 levels. Conclusions:High expression of serum pattern recognition receptors Collectin, Dectin and CD14 in children with hand, foot and mouth disease is closely related to the immune response, inflammatory response and target organ function damage during the disease progression.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Fluoroquinolone-macrolide combination therapy for chronic bacterial prostatitis： retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category Ⅱ chronic bacterial prostatitis （CBP）. The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin （500 rag, thrice-weekly） with a once-daily 500- or 750-mg dose of ciprofloxacin （Cipro-500 or Cipro-750 cohort, respectively）. Combined administration of azithromycin （1500 mg week^-1） with ciprofloxacin at the rate of 750 mg day^- 1 for 4 weeks rather than at 500 mg day^- 1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen （PSA） were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction （ED） at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

Cauda equina arachnoiditis–a rare manifestation of West Nile virus neuroinvasive disease:A case report

BACKGROUND Data regarding the neuroradiology features of the West Nile virus neuroinvasive disease(WNV NID)is rather scarce.To contribute to the knowledge of the WNV NID,we present a patient with a combination of encephalitis and acute flaccid paresis,with cauda equina arachnoiditis as the main magnetic resonance(MR)finding.CASE SUMMARY A 72-year-old female patient was admitted due to fever,headache and gait instability.During the first several days she developed somnolence,aphasia,urinary incontinence,constipation,and asymmetric lower extremities weakness.Cerebrospinal fluid analysis indicated encephalitis.Native brain computed tomography and MR were unremarkable,while spinal MR demonstrated cauda equina enhancement without cord lesions.Virology testing revealed WNV IgM and IgG antibodies in serum and cerebrospinal fluid,which confirmed acute WNV NID.The treatment was supportive.After two months only a slight improvement was noticed but cognitive impairment,loss of sphincter control and asymmetric inferior extremities weakness remained.The patient died after a month on chronic rehabilitation.CONCLUSION Cauda equina arachnoiditis is a rare,but possible neuroradiological feature in acute flaccid paresis form of WNV NID.

Best therapy for the easiest to treat hepatitis C virus genotype 1binfected patients

BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patients completed therapy irrespective of the drug regimen.At least one adverse effect occurred in 10.9%-36.3%and most of them were mild.No treatment related deaths have been reported.CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens.Positive predictors of SVR were female sex,absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.

DOUBLE IMMUNOCYTOCHEMICAL STAINING FOR HBsAg AND HBcAg IN HEPATOCELLULAR CARCINOMA AND SURROUNDING NONTUMOROUS LIVER TISSUE

A double immunocytochemical staining method was used to demonstrate HBsAg and HBcAg simultaneously in the same sections of 58 hepatocellular carcinomas. Several tumor cells contained both HBsAg and HBcAg. These results demonstrate that hepatitis B virus (HBV) DNA in tumor cells can simultaneously express both HBsAg and HBcAg and suggest the production of a complete virus by these cells. Cytoplasmic membranous HBcAg was found not only in well differentiated hepatocellular carcinoma but also in moderate and poorly differentiated hepatocellular carcinoma. The localization of HBcAg in tumor cells appears to be the same as that of surrounding nontumorous liver tissue.

Exploration and Research on HIV/AIDS Patients’ Complement C1q Level Changes before and after Treatments

Objective: The study aimed to investigate the complement C1q test results of HIV/AIDS patients in clinical application before and after treatments. Methods: We collected HIV/AIDS patients’ serum specimens storing at -80 centigrade freezer in cryogenic refrigerator for standby. After samples quantity met the requirements of selected cases unified, complement C1q was detected by immune transmission turbidity method, and compared the differences in complement C1q of HIV/AIDS patients in test results before and after treatment. In the collection of 96 cases selected samples, concentration of complement C1q was 157.95 ± 31.46 mg/L before treatment, while after treatment, it was 147.26 ± 28.76 mg/L. Comparing the results before and after treatment,?t?= 2.45726,?P?= 0.01049, the difference was statistically significant. Concentration of complement C1q increased after treatment with 33 cases. There were 63 cases reducing. Through statistical analysis on the data from the number of reducing and increasing cases, chi-square = 18.75,?P?= 0.00356, the difference was statistically significant. Complement C1q detection in the treatment of patients with HIV/AIDS had an important clinical significance in the process. The analysis of the concentration changes before and after treatment was clinically significant for drug selection and monitoring disease progression and curative effects, which would be worth further researching.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

流感与COVID-19患者的免疫球蛋白G糖基化差异

The essential role of immunoglobulin G(IgG)in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the fragment crystallizable(Fc)domain that occur under such circumstances.These glycans impact the antibody stability,half-life,secretion,immunogenicity,and effector functions.Therefore,in this study,we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits(sialylation,galactosylation,fucosylation,and bisecting Nacetylglucosamine(GlcNAc))—of 64 patients with influenza,77 patients with coronavirus disease 2019(COVID-19),and 56 healthy controls.Our study revealed a significant decrease in IgG galactosylation,sialylation,and bisecting GlcNAc(where the latter shows the most significant decrease)in deceased COVID19 patients,whereas IgG fucosylation was increased.On the other hand,IgG galactosylation remained stable in influenza patients and COVID-19 survivors.IgG glycosylation in influenza patients was more time-dependent:In the first seven days of the disease,sialylation increased and fucosylation and bisecting GlcNAc decreased;in the next 21 days,sialylation decreased and fucosylation increased(while bisecting GlcNAc remained stable).The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses,while the observed changes in deceased COVID-19 patients may indicate its deviation.

Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era

BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of therapy.Our study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free era.AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers.The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database.The measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to follow-up.Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment course.RESULTS The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of men.The decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications.Treatment-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in 2021.Genotype(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years.The effectiveness of the therapy was comparable regardless of the period analyzed,and patients achieved an overall response rate of 95%,with an SVR range of 72.9%-100%for the different therapeutic regimens.Male gender,GT3 infection,and prior treatment failure were identified as independent negative predictors of therapeutic success.CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens,confirming the high effectiveness of IFN-free therapy in all analyzed periods.

Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.

Is liver biopsy still needed in children with chronic viral hepatitis?

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression(grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies(elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

Single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population

BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.

Clinical,radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis

Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible.

Immune responses of dendritic cells combined with tumor-derived autophagosome vaccine on hepatocellular carcinoma

Background： To induce and collect tumor-derived autophagosomes （DRibbles） from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. Methods： Dendritic cells （DCs） generated from peripheral blood mononuclear cell （PBMC） of hepatocellular carcinoma （HCC） patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. Results： DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay （ELISA） showed that IFN-γ, levels after vaccination increased than before in most patients, but CDS＋ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ, were detected in the CD8＋ cells than CD4＋ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8＋ T cell responses, supporting it as a tumor vaccine candidate. Conclusions： Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Tuberculosis and hematopoietic stem cell transplant: Review of a difficult and often underestimated problem

Recipients of solid organ transplants(SOT) and stem cell transplants(SCT) constitute a group of patients at risk for tuberculosis(TB) development. The prevalence of active TB in patients undergoing SOT is higher than in patients undergoing SCT, probably due to the shorter period of immunosuppression in the latter. We reviewed the importance of SCT in individuals with hematological malignancies. Most TB cases occur in transplant patients by reactivation of latent infection after immunosuppression, most often within the first year after transplant, leading to graft loss and in some cases, death. Relevant variables to assess the risk of TB infection in a transplant recipient include the donor's and recipient's medical histories, imaging results, microbiology and tuberculin skin test(TST) and interferon-gamma release assays(IGRA). TST is routinely performed in the donor and recipient before transplantation. If TST is > 5 mm in the recipient or > 10 mm in the donor, it is necessary to exclude active TB(pulmonary and renal). Chemopro-phylaxis is recommended in TST(+) recipients and in recipients with recent seroconversion, in donors with a history of untreated TB or in contact with an individual with active TB, if radiological images are suspicious and the IGRA is(+). The drug of choice is isoniazid. These topics are herewith reviewed.

HIV/HCV Co-Infection—A Dual Neurocognitive Problem

Presence of the hepatitis C virus in HIV infected patients has an additional neurotoxic influence on the Central Nervous System. It has been described that HCV co-infection leads to neuropsychological impairment whose severity is greater than in mono-HIV infected subjects. In the present study we assessed the neuropsychological status of 46 human immunodeficiency virus (HIV)-infected individuals from the Warsaw Hospital for Infectious Diseases. For the purpose of cognitive assessment, neuropsychological tests measuring global cognitive functions, attention and perception, verbal memory, as well as non-verbal aspects of executive functions, e.g. visual monitoring and planning, were assessed. In 60% of the investigated patients, who were co-infected with the hepatitis C virus, the overall cognitive outcome observed was worse than in mono-HIV infected subjects. The following factors were taken into account: ART therapy’s influence on cognitive functions using the CPE rank (CNS Penetration Efficacy, 2010), route of HIV transmission, conditions of human existence and age of investigated patients. The present work should be treated as a preliminary research and interpreted in the context of several limitations described in the text.

Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection

Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.

Parvovirus B19 status in liver,kidney and pancreas transplant candidates:A single center experience

BACKGROUND Parvovirus B19(B19V)is associated with a wide range of clinical manifestations.The major presentation is erythema infectiosum.However,a persistent infection may cause pure red cell aplasia and chronic anemia in immunocompromized patients.The B19V seroprevalence varies with age and geographical location.AIM To determine the B19V serological status and DNAemia in kidney,liver,and pancreas transplant candidates.METHODS Patients who underwent kidney,liver,or simultaneous kidney and pancreas/liver transplantation between January 2021 and May 2022 were included in the study.The serum samples were collected before transplantation.For detection of B19V DNA,a LightMix Kit B19V EC(TIB MOLBIOL,Berlin,Germany)was used.B19V IgM and IgG antibodies were detected using a commercial ELISA test(Euroimmun,Lübeck,Germany).RESULTS One hundred and thirty-one transplant candidates were included in the study,71.0%male,with an average age of 53.27 years±12.71 years.There were 68.7%liver,27.5%kidney,3.0%simultaneous pancreas/kidney transplant(SPKT),and 0.8%simultaneous liver/kidney transplant recipients.No patients had detectable B19V DNA.B19V IgG seroprevalence was 77.1%.No acute or recent infections were detected(IgM antibodies).There was no difference in the mean age of seronegative and seropositive patients(51.8 years±12.9 years vs 53.7 years±12.7 years,t=-0.603;P=0.548).Although seropositivity was lower in patients aged less than 30 years(66.6%)compared to the patients aged 30-59 years and>60 years(80.4%and 78.1%,respectively),this difference was not significant.In addition,there was no difference in seropositivity between male and female transplant candidates,76.3%and 78.9%(χ^(2)=0.104;P=0.748).The seroprevalence did not differ among organ recipients,with 77.8%,80.6%,and 50.0%for liver,kidney,and SPKT,respectively,(χ^(2)=5.297;P=0.151).No significant difference was found in the seroprevalence in kidney transplant patients according to dialysis modality.Seroprevalence was 71.1%in hemodialysis patients,and 100%in peritoneal dialysis patients(χ^(2)=0.799;P=0.372).CONCLUSION The B19V seroprevalence is expectedly high among kidney,liver,and pancreas transplant candidates,but there are still 22.9%of seronegative individuals who remain at risk for primary disease and severe manifestations.Further research should elucidate the necessity of B19V screening in peri-transplant management.