Differential alterations of CXCR3, CXCR5 and CX3CR1 in patients with immune thrombocytopenia.

As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9-11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman's correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.

Exploration of biomarkers for systemic lupus erythematosus by machine-learning analysis.

BACKGROUND: In recent years, research on the pathogenesis of systemic lupus erythematosus (SLE) has made great progress. However, the prognosis of the disease remains poor, and high sensitivity and accurate biomarkers are particularly important for the early diagnosis of SLE. METHODS: SLE patient information was acquired from three Gene Expression Omnibus (GEO) databases and used for differential gene expression analysis, such as weighted gene coexpression network (WGCNA) and functional enrichment analysis. Subsequently, three algorithms, random forest (RF), support vector machine-recursive feature elimination (SVM-REF) and least absolute shrinkage and selection operation (LASSO), were used to analyze the above key genes. Furthermore, the expression levels of the final core genes in peripheral blood from SLE patients were confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. RESULTS: Five key genes (ABCB1, CD247, DSC1, KIR2DL3 and MX2) were found in this study. Moreover, these key genes had good reliability and validity, which were further confirmed by clinical samples from SLE patients. The receiver operating characteristic curves (ROC) of the five genes also revealed that they had critical roles in the pathogenesis of SLE. CONCLUSION: In summary, five key genes were obtained and validated through machine-learning analysis, offering a new perspective for the molecular mechanism and potential therapeutic targets for SLE.

T-cell senescence: A crucial player in autoimmune diseases.

Senescent T cells are proliferative disabled lymphocytes that lack antigen-specific responses. The development of T-cell senescence in autoimmune diseases contributes to immunological disorders and disease progression. Senescent T cells lack costimulatory markers with the reduction of T cell receptor repertoire and the uptake of natural killer cell receptors. Senescent T cells exert cytotoxic effects through the expression of perforin, granzymes, tumor necrosis factor, and other molecules without the antigen-presenting process. DNA damage accumulation, telomere damage, and limited DNA repair capacity are important features of senescent T cells. Impaired mitochondrial function and accumulation of reactive oxygen species contribute to T cell senescence. Alleviation of T-cell senescence could provide potential targets for the treatment of autoimmune diseases.

The role of adiponectin for immune cell function in metabolic diseases.

Adiponectin, as an indispensable regulator of the immune system, is the most abundant adipokine and is mainly produced by white adipose tissue. Adiponectin mediates the positive effects on systemic metabolism by regulating associated downstream signalling pathways; however, accumulating evidence shows that adiponectin plays an important role in regulating the function of innate and adaptive immune cells in the development of obesity and its related diseases. In this review, we focus on the biological function of adiponectin in regulating innate and adaptive immunity and outline the key role of adiponectin in various metabolic diseases, which will highlight a potential direction for adiponectin-based therapeutic interventions for metabolic diseases.

Development and clinical validation of a one-step pentaplex real-time reverse transcription PCR assay for detection of hepatitis virus B, C, E, Treponema pallidum, and a human housekeeping gene.

BACKGROUND: With the safety of blood transfusion being a major public health concern, the development of a rapid, sensitive, specific, and cost-effective multiplex PCR assay for simultaneous detection of hepatitis B virus(HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and Treponema pallidum(T. pallidum) in blood is crucial. METHODS: Five primer pairs and probes were designed towards conserved regions of target genes and used to establish a one-step pentaplex real-time reverse transcription PCR(qRT-PCR) assay for simultaneous detection of HBV, HCV, HEV, T. pallidum, and RNase P(housekeeping gene), providing sample quality check. The clinical performance of the assay was further determined with 2400 blood samples from blood donors and patients in Zhejiang province, and compared the results with commercial singleplex qPCR and serological assays. RESULTS: The 95% limit of detection(LOD) of HBV, HCV, HEV, and T. pallidum were 7.11 copies/µL, 7.65 copies/µL, 8.45 copies/µL, and 9.06 copies/µL, respectively. Moreover, the assay has good specificity and precision. Compared to the singleplex qPCR assay, the novel assay for detecting HBV, HCV, HEV, and T. pallidum presented 100% clinical sensitivity, specificity, and consistency. Several discrepant results between serological and pentaplex qRT-PCR assays were found. Of 2400 blood samples, there were 2(0.08%) HBsAg positive samples, 3(0.13%) anti-HCV positive samples, 29(1.21%) IgM anti-HEV positive samples and 6(0.25%) anti-T. pallidum positive samples proven negative in nucleic acid detection. 1(0.04%) HBV DNA positive sample and 1(0.04%) HEV RNA positive sample were detected negative by serological testing. CONCLUSIONS: The developed pentaplex qRT-PCR is the first assay on simultaneous, sensitive, specific, and reproducible detection of HBV, HCV, HEV, T. pallidum, and RNase P in a single tube. It could detect pathogens in blood during the window period of infection and is a good tool for effectively screening blood donors and early clinical diagnosis.

Surgical Efficacy among Laparoscopic Ultrasonic Dissectors in Adenomyosis.

OBJECTIVES: The present study aimed to investigate the efficacy of ultrasonic dissectors for adenomyomectomy using the double/multiple-flap method combined with temporary occlusion of the temporary bilateral uterine artery and the utero-ovarian vessels for the treatment of symptomatic adenomyosis. DESIGN: This was a retrospective study. PARTICIPANTS: In total, 162 patients with symptomatic adenomyosis were included, and all of them had originally been scheduled to group A (n = 82) and group B (n = 80) with each group representing a different surgical application. All eligible women were informed of the potential complications, benefits, and alternatives of each approach before they were assigned to one of the two groups, and patients chose group A or group B by themselves. In group A, we performed laparoscopic ultrasonic dissectors in adenomyosis with the double/multiple-flap method combined with temporary occlusion of the bilateral uterine artery and utero-ovarian vessels, while in group B, we performed adenomyomectomy with scissors. During the period of treatment, we evaluated operative time, intraoperative blood loss, and the degree of fatigue of surgeons' fingers. RESULTS: The estimated blood loss, operative time, and the degree of fatigue of surgeons' fingers in group A were significantly lower than that in group B (p < 0.001). No serious perioperative complications were observed in either group. LIMITATIONS: This was a retrospective study. CONCLUSION: The use of ultrasonic dissectors in laparoscopic adenomyomectomy with temporary occlusion of the bilateral uterine artery and the utero-ovarian vessels leads to improvements and releases the fatigue of surgeons' fingers in laparoscopic adenomyomectomy.

Optimum Control for Path Tracking Problem of Vehicle Handling Inverse Dynamics.

Accurate tracking of a given path is one of the primary factors in the maneuverability of a vehicle and is also an important topic in autonomous vehicle research. To solve the problem of vehicle path tracking, the problem must first be transformed into an optimal control problem. Then, a symplectic pseudospectral method (SPM) based on the third-generation function of symplectic theory and pseudospectral discretization is proposed to efficiently solve the nonlinear optimal control problems. Finally, the results obtained by the proposed algorithm are compared with those obtained by the Gauss pseudospectral method (GPM). The simulation results show that the proposed method can effectively solve the vehicle path tracking problem. Furthermore, the vehicle can track the given path controlled by the proposed algorithm with higher accuracy and greater applicability than other methods.

Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is characterized by the presence of dysfunctional exhausted CD8+ T cells that hamper viral control. We investigated the phenotypic heterogeneity of exhausted CD8+ T cells in HBV carriers. METHODS: We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8+ T cell subsets. Expression of cytokines such as TNF-α and IFN-γ was detected by quantitative reverse transcription-PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry. RESULTS: There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8+ T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (P < 0.05); in particular, Tfc cells (CXCR5+CD25-) expressed higher levels of TIM3 and PD1 than non-Tfc cells in the HBV carriers. In addition, among the subsets of Tc cells, the Tc17 (CXCR5-CD25-CCR6+) subset displayed increased expression of TIM3 and LAG3 in the HBV carriers. Our findings further showed that CD8+ T cells produced lower levels of IFN-γ, TNF-α, and Granzyme B. Paired analysis of the Tfc subset and the Tc subset indicated that higher levels of cytokines (IFN-γ and TNF-α) were produced by the Tfc subset in the HBV carriers. Among the Tc subsets, the Tc17 subset produced lower levels of cytokines. CONCLUSION: The Tfc subset exhibited an enhanced exhausted phenotype but possessed some functional properties during chronic HBV infection, while the Tc subset showed a lower functional level. The identification of these unique subsets may provide a potential immunotherapeutic target in chronic HBV infection.

mTOR signaling: A pivotal player in Treg cell dysfunction in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by multiorgan involvement and marked variability in clinical presentation. SLE pathogenesis includes regulatory T cell dysfunction and antinuclear antibody production. Mammalian target of rapamycin (mTOR), a serine/threonine kinase in the phosphoinositide 3-kinase (PI3K)-related kinase family, is a therapeutic target for autoimmune diseases such as SLE. Rapamycin, an inhibitor of the mTOR signaling pathway, is a macrolide antibiotic with potent immunosuppressive, antiproliferative and antifibrotic effects. Recently, an increasing number of studies have investigated the role of mTOR in regulatory T (Treg) cells and its impact on SLE pathogenesis. This review aims to systematically summarize the role of the mTOR signaling pathway in SLE pathogenesis, Treg cell dysfunction and SLE treatment.

Relationship between Blood Lipid Profiles and Risk of Lupus Nephritis in Children.

Objective: Systemic lupus erythematosus (SLE) is a relatively common rheumatic disease in children. The characteristics of blood lipid metabolism in children with LN are little reported. This study aimed to explore the relationship between blood lipid profiles and the risk of lupus nephritis (LN) in children. Methods: A total of 134 children with newly diagnosed SLE were divided into LN and non-LN groups according to pathological renal biopsy results. Clinical manifestations and blood lipid profiles were analyzed and compared between the two groups, and the relationships between blood lipid profiles and risk of LN were evaluated. Results: The positivity rate of an anti-dsDNA antibody and an SLE disease activity index (SLEDAI) were significantly increased, and C3 and C4 levels were significantly reduced in the LN compared with the non-LN group. The overall incidence of dyslipidemia was 79.9%, with a significantly high incidence in the LN group compared with the non-LN group. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very LDLC (VLDL-C) were all higher in the LN group than those in the non-LN group. However, there was no significant difference in high-density lipoprotein cholesterol (HDL-C) between the two groups. The blood lipid levels were positively correlated with 24-hour urine protein quantification, urea, creatinine, uric acid, urinary IgG, urinary microalbumin, urinary transferrin, urinary α1 microglobulin, and urinary N-acetyl glucosidase, respectively. Receiver-operating characteristic curves showed that combined detection of TC, TG, LDL-C, and VLDL-C had higher discrimination capacity than that in individual measures. Additionally, increased TC was independently associated with the occurrence of LN. Conclusions: Children with LN have significant dyslipidemia. High levels of TC, TG, LDL-C, and VLDL-C are closely related to the occurrence of pLN. Clinical attention should be paid to monitoring and managing blood lipid profiles in children with LN.

Analysis of the Complete Genomes of Enterovirus 71 Subtypes in China.

Enterovirus 71 (EV-A71) is one of the most pathogens to hand, foot, and mouth disease (HFMD) as well as neurological complications in young children. Molecular characteristic of EV-A71 is important to prevent the virus outbreak. Here, the complete genomes of EV-A71 from China between 1998 and 2019 were downloaded from GenBank. The phylogenetic trees were developed by MEGA7.0 software, and the complete genetic epidemiological characteristics and amino acid mutations of EV-A71 from China were also analysed. The results showed that major epidemic EV-A71 subtype was C4b before 2004, while it turned to C4a after 2004 in mainland China, and C4 and B5 were major subtypes in Taiwan. VP1, VP4, 2C, 3C, 3D, and complete genome sequence can be used for virus genotyping, and VP1, VP4, and complete genomes have obvious advantages over other segments. There were many significant mutations in the viral complete genome sequence. This study indicated that the major C4 and B5 subtypes will contribute to the development of vaccines and drugs of EV-A71 for prevention and monitoring of EV-A71-associated HFMD in China.

Elevated expansion of follicular helper T cells in peripheral blood from children with acute measles infection.

BACKGROUND: Measles outbreaks have threatened the global elimination and eradication of measles in recent years. Measles virus (MeV)-specific antibodies are successful in clearing MeV infection. Follicular helper T (Tfh) cells play a crucial role in promoting antibody production. This study investigated the potential role of Tfh cells in peripheral blood mononuclear cells (PBMCs) from children with acute MeV infection. RESULTS: The frequencies of CXCR5+CD4+ Tfh, ICOShigh Tfh, and PD-1high Tfh cells in PBMCs and levels of IL-6 and IL-21 in plasma were significantly elevated in patients with acute MeV infection. Moreover, a positive correlation was discovered among the frequency of ICOShigh Tfh cells, plasma levels of IL-21 and optical density (OD) values of MeV-specific IgM antibodies in the patients with acute MeV infection. However, elevated plasma MeV-specific NAb titres were not associated with the frequency of Tfh, ICOShigh Tfh, or PD-1high Tfh cells in the patients with acute MeV infection. CONCLUSION: These results suggest that an elevated Tfh cell frequency and associated molecules possibly play a key role in children with acute MeV infection, which contributes to the prevention and treatment of MeV infection in children.

Etiological analysis of virus, mycoplasma pneumoniae and chlamydia pneumoniae in hospitalized children with acute respiratory infections in Huzhou.

BACKGROUND: Acute respiratory infections are a common disease in children with high mortality and morbidity. Multiple pathogens can cause acute respiratory infections. A 2-year survey of hospitalized children was conducted to understand the epidemic situation, seasonal spread of pathogens and the improvement of clinical diagnosis, treatment and prevention of disease in Huzhou, China. METHODS: From September 2017 to August 2019, 3121 nasopharyngeal swabs from hospitalized children with acute respiratory infections were collected, and real-time PCR was used to detect various pathogens. Then, pathogen profiles, frequency and seasonality were analyzed. RESULTS: Of the 3121 specimens, 14.45% (451/3121) were positive for at least one pathogen. Of the single-pathogen infections, RSV (45.61%, 182/399) was the most frequent pathogen, followed by PIVs (14.79%, 59/399), ADV (14.54%, 58/399), MP (10.78%, 43/399), and IAV (5.26%, 21/399). Of the 52 coinfections, RSV + PIVs viruses were predominantly identified and accounted for 40.38% (21/52) of cases. RSV was the most frequent pathogen in all four groups. The highest positive rate of the pathogens occurred in the winter (21.26%), followed by autumn (14.98%), the summer (14.11%) and the spring (12.25%). CONCLUSION: Viruses are the main pathogens in hospitalized children with acute respiratory infections in Huzhou city, Zhejiang Province, China. Among the pathogens, RSV had the highest detection rate, and MP is also a common pathogen among children with acute respiratory infections. This study provided a better understanding of the distribution of pathogens in children of different ages and seasons, which is conducive to the development of more reasonable treatment strategies and prevention and control measures.

A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic.

A sensitive and specific diagnosis biomarker, in principle scalable to most cancer types, is needed to reduce the prevalent cancer mortality. Meanwhile, the investigation of diagnosis determinants of a biomarker will facilitate the interpretation of its screening results in clinic. Here we design a large-scale (1558 enrollments), multicenter (multiple hospitals), and cross-validation (two datasets) clinic study to validate plasma Hsp90α quantified by ELISA as a pan-cancer biomarker. ROC curve shows the optimum diagnostic cutoff is 69.19 ng/mL in discriminating various cancer patients from all controls (AUC 0.895, sensitivity 81.33% and specificity 81.65% in test cohort; AUC 0.893, sensitivity 81.72% and specificity 81.03% in validation cohort). Similar results are noted in detecting early-stage cancer patients. Plasma Hsp90α maintains also broad-spectrum for cancer subtypes, especially with 91.78% sensitivity and 91.96% specificity in patients with AFP-limited liver cancer. In addition, we demonstrate levels of plasma Hsp90α are determined by ADAM10 expression, which will affect Hsp90α content in exosomes. Furthermore, Western blotting and PRM-based quantitative proteomics identify that partial false ELISA-negative patients secret high levels of plasma Hsp90α. Mechanism analysis reveal that TGFß-PKCγ gene signature defines a distinct pool of hyperphosphorylated Hsp90α at Theronine residue. In clinic, a mechanistically relevant population of false ELISA-negative patients express also higher levels of PKCγ. In sum, plasma Hsp90α is a novel pan-cancer diagnosis biomarker, and cancer diagnosis with plasma Hsp90α is particularly effective in those patients with high expression of ADAM10, but may be insufficient to detect the patients with low ADAM10 and those with hyperphosphorylated Hsp90α.

Clinical characteristics and viral etiologies of outpatients with acute respiratory infections in Huzhou of China: a retrospective study.

BACKGROUND: Viruses are commonly found in patients with acute respiratory infections (ARIs). However, the viral etiologies and clinical characteristics of outpatients with ARIs are poorly understood in China. Here, we identified the viral etiologies in outpatients with ARIs in Huzhou, China. RESULTS: Our results indicated that of 426 outpatients, 246 were positive for viruses. Of them, 221 were positive for a single virus, including influenza A, which comprised H3N2 (28.5%) and pandemic H1N1 (2009) (19.0%), enterovirus (10.4%), and influenza B (8.6%). Other single viruses were detected at less than 8.0%. Twenty-five patients were positively coinfected with two viruses. The prevalent viruses in coinfections were rhinovirus and H3N2 virus (28.0%). Viruses were major pathogens in young children (< 5 years) (75.0%). Coinfections were prevalent in older adults (11.9%) and young children (9.5%). Virus-positive outpatients presented higher temperatures and more sore throat, fatigue and shortness of breath than virus-negative outpatients. ARIs and most virus detections peaked during the winter, but enteroviruses emerged between April and September. CONCLUSION: Viruses are major agents of ARIs among outpatients in Huzhou, China. There was a variation in the distribution of viruses across different age groups and seasons. These findings are beneficial for planning prevention and treatment services for outpatients with ARIs.

Benefit of Early Initiation of Neuraminidase Inhibitor Treatment to Hospitalized Patients With Avian Influenza A(H7N9) Virus.

Background: The significance of early neuraminidase inhibitor (NAI) therapy for treating influenza A(H7N9) is currently unknown. Methods: The duration of viral shedding was monitored by reverse-transcription polymerase chain reaction after patients with confirmed H7N9 infection were admitted to the First Affiliated Hospital, Zhejiang University, during April 2013-April 2017. Indices such as the length of hospitalization and mortality were collected, and the correlation between the time of administration of NAI and the severity of disease was systematically analyzed. Results: One hundred sixty patients with confirmed H7N9 infection were divided into 3 groups according to NAI starting time. Three of 20 (15%) patients for whom NAI was administered within 2 days died compared with 12 of 52 (23.1%) patients who received treatment within 2-5 days and 33 of 88 (37.5%) patients who were treated after 5 days (P < .05). The median durations of viral shedding from NAI therapy initiation was 4.5 days (interquartile range [IQR], 3-9 days) for patients who took antiviral medication within 2 days, which was significantly different from that for patients who took medication within 2-5 days (7.5 days [IQR, 4.25-12.75 days]) or after 5 days (7 days [IQR, 5-10 days]) (P < .05). We found that the duration of viral shedding from NAI therapy was the shortest in spring 2013 (5.5 days) and the longest in winter-spring 2016-2017 (8.5 days) (P < .05), showing a prolonged trend. Conclusions: Early NAI therapy within 2 days of illness shortened the duration of viral shedding and improved survival in patients with H7N9 viral infection.

A novel general and efficient technique for dissociating antigen in circulating immune complexes.

Circulating immune complexes (CICs) are produced during the immune response. It is more clinically important to establish a general and efficient CICs dissociation technique for the detection of antigens for CICs other than the detection of free antigens in the serum. Polyethylene glycol (PEG) two-precipitation separation and glycine-HCl as a buffer system were employed to develop a general and efficient buffer dissociation technique to separate CICs from serum and dissociate antigens from CICs. The measurement value of new PEG two-precipitation separation technique was higher than traditional PEG precipitation separation technique. There were slight differences in the dissociation conditions of HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC as compared to HBsAg-IC. The detection of antigens in HBsAg-IC, HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC with this technique was superior to that with HCl Dissociation, Trypsin Digestion or Immune Complex Transfer technique. PEG two-precipitation dissociation technique may reduce macromolecular protein and the adhesion of free antigens during the co-precipitation, which increases the efficiency of separation and precipitation of CICs. This technique also avoids the damage of reagents to antigens, assuring the repeatability, reliability and validity. Thus, this technique is application in samples negative or positive for free antigens.

Genetic characteristics of the P1 coding region of Coxsackievirus A16 associated with hand, foot, and mouth disease in China.

Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot, and mouth disease (HFMD) in young children. To investigate the genetic characteristics of the P1 coding region gene of CVA16 associated with HFMD in China, we included the sequences of CVA16 specimens obtained from outbreak investigations and sporadic HFMD cases between 1998 and 2014 in China from GenBank, we genotyped the CVA16 sequences and analyzed P1 coding region sequences that encode structural proteins with bioinformatics software. CVA16 was classified into genotypes A and B1 based on the VP1 gene; the B1b and B1a subgenotypes were the major CVA16 strains and predominated in the coastal areas of China. Four strains were found to show inter- and intra-typic recombination in the P1 region. The amino acid identities of VP1, VP2, VP3, and VP4 proteins in all Chinese CVA16 strains were 88.2-100%, 83.0-100%, 87.6-100%, and 72.4-100%, respectively. A total of 251 amino acid substitution sites were detected in the structural proteins encoded by the P1 coding region gene. The amino acid sequences of the P1 coding region in Chinese CVA16 strains were highly conserved, although some amino acid mutations occurred with high frequency: VP1-T11A (10%), N14S (14%), L23M/V (11%), T98M (16%), V107A (14%), N102D (6.1%), E145V (8.8%), N218D (10%), E241K (22%), T248A/I (6.8%); VP2-I217V (22%), T226A (38%); VP3-N141S/G (5.4%), and N240D (15%). The genetic characteristics of CVA16 in the P1 coding region gene may provide a basis for developing a CVA16 vaccine and preventing and controlling HFMD in China.

The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR. RESULTS: At the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered. CONCLUSION: These findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

Analysis of epidemiological trends in human papillomavirus infection among gynaecological outpatients in Hangzhou, China, 2011-2015.

BACKGROUND: HPV infection is the major pathogenic factor underlying cervical cancer and precancerous lesions. The cervical HPV infection rates in gynaecological outpatients from Hangzhou, China, were studied in the period from January 2011 to December 2015. METHODS: Exfoliated cervical cells were harvested from gynaecological outpatients in Hangzhou from January 2011 to December 2015. Twenty-one HPV subtypes were detected using flow-through hybridization. The HPV infection rates in various disease groups were compared using the Chi-square test. The infection rates of different HPV subtypes in different calendar years and in different age groups were analysed using the linear-by-linear association test and gamma value. RESULTS: A total of 43,804 patients were recruited, of whom 9752 (22.3%) were infected with HPV. The top five among the 21 HPV subtypes detected in terms of infection rates were HPV-16, -52, -58, -53 and -18. No significant differences (linear-by-linear association test) were found in the HPV infection rates when compared over the studied years (P > 0.05). However, the 15-24-year-old age group showed the highest HPV infection rate, and significant differences (linear-by-linear association test) were detected among the different age groups (P < 0.05). The HPV infection rates exhibited an upward trend in the 15-24-year-old and >24-34-year-old groups over the past five years. There were significant differences in the HPV infection rates among the disease groups (P < 0.05). CONCLUSIONS: HPV-16, -52 and -58 were the major HPV infection subtypes in Hangzhou, China. The 15-24-year-old age group had a relatively high HPV infection rate with an upward trend over the past five years and thus represented a population susceptible to HPV infection.