Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study.

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

Could ceftriaxone be a viable alternative to penicillin for the treatment of ocular syphilis?

This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.

Clinical parameter-based prediction model for neurosyphilis risk stratification.

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83-0.85) and 0.82 (95% CI, 0.78-0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.

Clinical Characteristics and Prognosis of Infants and Children <3 Years of Age With Thyroglossal Duct Cyst Complicated With a Parapharyngeal Mass: A Case Series Study.

Thyroglossal duct cysts (TGDCs) are congenital and developmental abnormalities in infants and young children. This retrospective case series study examined the characteristics of 7 patients <3 years (mean age, 1.9 years) with TGDC complicated with a parapharyngeal mass treated at one hospital between January 2019 and 2022. Four patients had a painless mass around the neck, 2 had a painless mass associated with snoring, and 1 presented repeated swelling and pain. B-ultrasound suggested 6 cases of TGDC and 1 possible lymphangioma. All patients were treated with Sistrunk surgery to remove the TGDC. Six patients had no cyst recurrence during follow-up (6 months to 2 years). In conclusion, TGDC complicated with a parapharyngeal mass has complex and variable clinical manifestations. Completely removing the cyst while sparing thyroid cartilage and surrounding vascular and neuroanatomical structures is important to avoid complications. The patients are likely to be free from recurrence after surgery.

Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.

BACKGROUND AND OBJECTIVES: Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear. METHODS: Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT ( n  = 48) and non-MHT ( n  = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease. RESULTS: Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ±â€Š13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints. CONCLUSIONS: Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.

The Role of Renal PLA2R Staining Combined with Serum PLA2R Antibody in Membranous Nephropathy Risk Stratification.

BACKGROUND: This study aimed to examine the clinicopathological profiles and prognosis of membranous nephropathy in different subtypes classified by serum PLA2R antibody (SAb) and glomerular PLA2R antigen staining (GAg). METHODS: A total of 372 biopsy-proven membranous nephropathy (MN) cases, unrelated to lupus, with urine protein > 2 g/24 h and eGFR > 25 mL/min/1.73 m2 were included and categorized into four groups according to the presence or absence of PLA2R antibody and glomerular PLA2R antigen staining. Clinical profiles were compared among four subtypes. Treatment response and renal outcomes were compared among four groups with primary MN. Cox and logistic regression models were used to examine the association between time-to-renal progression and early remission within 6 months in the four subgroups with primary MN. RESULTS: MN patients who were SAb-/GAg+ presented with a more severe disease onset, whereas those who were SAb-/GAg- had a mild clinical manifestation with a higher prevalence of MN-associated secondary causes. During a median follow-up of 79.2 months (IQR: 48.70-97.40), SAb+/GAg- was identified as an independent risk factor for renal progression [HR: 9.17, 95% CI: 2.26-37.16, p < 0.01] and early remission [OR: 0.06, 95% CI: 0.01-0.56, p = 0.01] in primary MN. Additionally, SAb-/GAg- with primary MN showed an independent association with spontaneous remission after adjusting for age, sex, baseline proteinuria, and eGFR (Before adjustment: OR: 8.33, 95% CI: 1.89-36.76, p = 0.0; after adjustment: OR: 12.25, 95% CI: 2.48-60.53, p < 0.01). CONCLUSION: Our findings indicated that SAb+/GAg-MN patients exhibited a more severe disease onset and had a poorer prognosis, necessitating an aggressive treatment approach. On the other hand, in the SAb-/GAg- group, the elimination of secondary causes should be considered, and a watchful waiting approach may be appropriate.

CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis.

BACKGROUND: Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN. METHODS: 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo-/- mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. RESULTS: The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p < 0.001), healthy controls (p < 0.001) and kidney function adjusted controls (p < 0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p < 0.05) and remissive patients (p < 0.01). Immunohistochemistry showed CD206 was highly expressed in different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904. CONCLUSION: ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease.

Delivery of Basic Fibroblast Growth Factor Through an In Situ Forming Smart Hydrogel Activates Autophagy in Schwann Cells and Improves Facial Nerves Generation via the PAK-1 Signaling Pathway.

Although studies have shown that basic fibroblast growth factor (bFGF) can activate autophagy and promote peripheral nerve repair, the role and the molecular mechanism of action of bFGF in the facial nerve are not clear. In this study, a thermosensitive in situ forming poloxamer hydrogel was used as a vehicle to deliver bFGF for treating facial nerve injury (FNI) in the rat model. Using H&E and Masson's staining, we found that bFGF hydrogel can promote the functional recovery and regeneration of the facial nerve. Furthermore, studies on the mechanism showed that bFGF can promote FNI recovery by promoting autophagy and inhibiting apoptosis. Additionally, this study demonstrated that the role of hydrogel binding bFGF in nerve repair was mediated through the activation of the PAK1 signaling pathway in Schwann cells (SCs). These results indicated that poloxamer thermosensitive hydrogel loaded with bFGF can significantly restore the morphology and function of the injured facial nerve by promoting autophagy and inhibiting apoptosis by activating the PAK1 pathway, which can provide a promising strategy for FNI recovery.

Platelet Indices Are the Promising Biomarkers in Monitoring Disease Activities in Patients with Syphilis.

OBJECTIVES: To uncover the role of the platelet indices in patients with syphilis. METHODS: A total of 2061 patients with syphilis and 528 healthy controls were enrolled in this retrospective cohort study. The data of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and indicators of syphilis activities were collected. The correlations between the platelet indices and disease activities were analyzed. RESULTS: A total of 425 (20.6%) of the 2061 patients were of primary and secondary syphilis, 433 (21.0%) latent, 463 (22.5%) serofast, 350 (17.0%) asymptomatic neurosyphilis, and 390 (18.9%) symptomatic neurosyphilis. Compared with the healthy controls, PLT was significantly increased in the primary and secondary syphilis group; whereas, MPV and PDW were significantly decreased in all stages of syphilis. These changes of platelet indices were reversed after anti-treponemal therapy. Further correlation analysis showed that PLT was positively associated with the syphilis activity indicators [rapid plasma reagin (RPR) titer, cerebrospinal fluid white blood cell (CSF-WBC), CSF-protein, and CSF-VDRL (venereal disease research laboratory)] and inflammatory markers [WBC, C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR)]. Conversely, PDW was negatively correlated with all of these parameters. MPV had an inverse relationship with RPR, ESR, and CRP. CONCLUSIONS: Platelet indices are associated with syphilis activities.

Effect of parasympathetic inhibition on expression of ILC2 cells in a mouse model of allergic rhinitis.

BACKGROUND: We wanted to investigate whether parasympathetic inhibition affected the expression of type 2 innate lymphoid cells (ILC2s) in the nasal mucosa of a mouse model of allergic rhinitis (AR). METHODS: Thirty male C57BL/6 mice were randomly divided into 3 groups: control group, AR group, AR-treated group. AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The expression of cytokines protein in serum was detected by enzyme linked immunosorbent assay (ELISA). The number of ILC2s in nasal mucosa was detected by immunofluorescence double staining assay. Quantitative real-time Polymerase Chain Reaction (qPCR) was used to detect the expression of ILC2-associated factor in nasal mucosa. RESULTS: The symptom scores of the AR group were significantly higher than those of the control group and AR-treated group. The expression levels of mouse ovalbumin (OVA) specific IgE, IL4, IL5, and IL13 in the serum of AR group were significantly higher than those in the control group and AR-treated group. The number of ILC2s and the gene expression of ILC2s related factors GATA3, CD25 and CD90 (Thy1) in the nasal mucosa of the AR group were significantly higher than those of the control group and AR-treated group. CONCLUSIONS: We found that parasympathetic inhibition relieved AR symptoms and inhibited immune response of AR mice. ILC2s play an important role in the occurrence and development of AR, and parasympathetic nerve inhibition reduced the number of ILC2s and inhibited the cytokines expression by ILC2s. Our data provide information on the mechanism of action of parasympathetic inhibition in AR.

Clinical safety and outcome of recombinant tissue plasminogen activator in patients with stroke attributable to small artery occlusion: A protocol for systematic review and meta-analysis.

BACKGROUND: Recent observations raised concern that the intravenous recombinant tissue plasminogen activator (rt-PA) may result in damage to stroke patients caused by small artery occlusion (SAO). Thus, we perform a protocol for meta-analysis to investigate the efficacy and safety of intravenous thrombolysis with rt-PA in SAO-patients. METHODS: The search-style electronic libraries, including Pubmed, Embase, the Cochrane Library, Web of Science, Wanfang Data, VIP Chinese Journals, and China Biomedical Literature Service System are used for document retrieval in June 2021 with no restrictions on language. The risk of bias in include articles will be assessed using the Cochrane Risk of Bias Tool. We perform the meta-analysis by Stata version 10.0 software and calculated the statistics using the inverse variance statistical method. Binary outcomes are presented as Mantel-Haenszel-style risk ratios with 95% confidence interval. Continuous outcomes are reported as mean differences. RESULTS: The results of the article will be shown in a peer-reviewed journal. CONCLUSION: Intravenous rt-PA may be effective and safe in SAO-patients.

Characterization of Two Macrolide Resistance-Related Genes in Multidrug-Resistant Pseudomonas aeruginosa Isolates.

In analyzing the drug resistance phenotype and mechanism of resistance to macrolide antibiotics of clinical Pseudomonas aeruginosa isolates, the agar dilution method was used to determine the minimum inhibitory concentrations (MICs), and PCR (polymerase chain reaction) was applied to screen for macrolide antibiotics resistance genes. The macrolide antibiotics resistance genes were cloned, and their functions were identified. Of the 13 antibiotics tested, P. aeruginosa strains showed high resistance rates (ranging from 69.5-82.1%), and MIC levels (MIC90 > 256 µg/ml) to macrolide antibiotics. Of the 131 known macrolide resistance genes, only two genes, mphE and msrE, were identified in 262 clinical P. aeruginosa isolates. Four strains (1.53%, 4/262) carried both the msrE and mphE genes, and an additional three strains (1.15%, 3/262) harbored the mphE gene alone. The cloned msrE and mphE genes conferred higher resistance levels to three second-generation macrolides compared to two first-generation ones. Analysis of MsrE and MphE protein polymorphisms revealed that they are highly conserved, with only 1-3 amino acids differences between the proteins of the same type. It can be concluded that even though the strains showed high resistance levels to macrolides, known macrolide resistance genes are seldom present in clinical P. aeruginosa strains, demonstrating that a mechanism other than this warranted by the mphE and msrE genes may play a more critical role in the bacteria's resistance to macrolides.

Comparative genomics analysis of Raoultella planticola S25 isolated from duck in China, with florfenicol resistance.

To characterize the florfenicol resistance gene and analyze the structure of the resistance gene-related sequence of an Raoultella planticola strain S25 isolated from a duck fecal sample from a farm in South China. Molecular cloning was performed to clone the resistance genes such as mdfA, floR and so on, and the minimum inhibitory concentrations (MICs) were quantified to determine the resistance levels generated by the cloned genes and the related strains. Sequencing and comparative genomics methods were used to analyze the structure of the resistance gene-related sequence. The result showed that the genome of R. planticola S25 consists of a 5.47 Mb chromosome encoding 4962 predicted coding sequence (CDS) and a 68,566 bp plasmid, pS25-68, encoding 84 ORFs. The plasmid sharing the greatest sequence identity with the floR-carrying plasmid pS25-68 is plasmid1 in Klebsiella pneumoniae strain blaNDM-1, which was isolated from a patient in Canada. The mdfA1 gene encoded on the chromosome generated resistance to florfenicol in addition to chloramphenicol. Comparative genomic analysis of the floR-related transposon-like fragment of pS25-68 showed that an approximately 3 kb sequence encoding IS91-virD2-floR-lysR was conserved and presented in the majority of the sequences (84.5 %, 169/200) collected from the database. The results of this work demonstrated that horizontal transfer of the florfenicol resistance gene floR occurred widely between the bacteria of different species and with different origins and that additional florfenicol resistance genes may be present in the bacterial population.

A Validation Study on eGFR Equations in Chinese Patients With Diabetic or Non-diabetic CKD.

Aims: It remains controversial to choose the optimal equation to estimate glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients with diabetes. Materials and Methods: Two hundred and fifteen diabetic CKD patients and 192 non-diabetic CKD patients were enrolled in this study. Iohexol GFR, serum creatinine (SCr), and Cystatin C(CysC) were measured simultaneously for each patient. SCr- and CysC-based estimated GFR (eGFR) were calculated through eight equations, including three CKD-EPI equations, Revised Lund-Malmö study equation (RLM), CAPA equation, and three Full Age Spectrum (FAS) equations. Bias, precision, and accuracy were compared among eGFR equations with iohexol-GFR serving as measured GFR (mGFR). Independent predictive factors of accuracy were explored using multivariate logistic regression analysis. Results: In the diabetic group, CKD-EPISCr-CysC showed the best performance among three CKD-EPI equations (interquartile range of 13.88 ml/min/1.73 m2 and 30% accuracy of 72.56%). Compared to CKD-EPISCr-CysC, the other five equations did not significantly improve the performance of GFR estimates. Mostly, eGFR equations were less accurate in diabetic group than in non-diabetic group. Significant differences were found in different mGFR range (P < 0.001). The multivariate logistic regression analysis identified that BMI, mGFR, and diabetic kidney disease (DKD) status were independent predictors of accuracy of three equations in diabetic group. HbA1c was a predictor of accuracy of CKD-EPISCr and CKD-EPICysC in diabetic group. Conclusions: This study showed that eGFR equations were less accurate in the diabetic group than in the non-diabetic group. CKD-EPIScr-CysC had the best performance among CKD-EPI equations in Chinese diabetic CKD patients. The other five equations did not significantly improve the performance of GFR estimates. BMI, mGFR, DKD status, and HbA1c were independent factors associated with accuracy in eGFR equations.

White blood cell count and the incidence of hyperuricemia: insights from a community-based study.

Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). The relationship between HUA and white blood cell (WBC) count remains unknown. A sampling survey for CKD was conducted in Sanlin community in 2012 and 2014. CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR of 60 mL/(min∙1.73 m2). HUA was defined as serum uric acid > 420 µmol/L in men and > 360 µmol/L in women. This study included 1024 participants. The prevalence of HUA was 17.77%. Patients with HUA were more likely to have higher levels of WBC count, which was positively associated with HUA prevalence. This association was also observed in participants without CKD, diabetes mellitus, hyperlipidemia, or obesity. Multivariate logistic regression analysis showed that WBC count was independently associated with the risk for HUA in male and female participants. Compared with participants without HUA, inflammatory factors such as high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin 6 increased in participants with HUA. Hence, WBC count is positively associated with HUA, and this association is independent of conventional risk factors for CKD.

Spread of the florfenicol resistance floR gene among clinical Klebsiella pneumoniae isolates in China.

Background: Florfenicol is a derivative of chloramphenicol that is used only for the treatment of animal diseases. A key resistance gene for florfenicol, floR, can spread among bacteria of the same and different species or genera through horizontal gene transfer. To analyze the potential transmission of resistance genes between animal and human pathogens, we investigated floR in Klebsiella pneumoniae isolates from patient samples. floR in human pathogens may originate from animal pathogens and would reflect the risk to human health of using antimicrobial agents in animals. Methods: PCR was used to identify floR-positive strains. The floR genes were cloned, and the minimum inhibitory concentrations (MICs) were determined to assess the relative resistance levels of the genes and strains. Sequencing and comparative genomics methods were used to analyze floR gene-related sequence structure as well as the molecular mechanism of resistance dissemination. Results: Of the strains evaluated, 20.42% (67/328) were resistant to florfenicol, and 86.96% (20/23) of the floR-positive strains demonstrated high resistance to florfenicol with MICs ≥512 µg/mL. Conjugation experiments showed that transferrable plasmids carried the floR gene in three isolates. Sequencing analysis of a plasmid approximately 125 kb in size (pKP18-125) indicated that the floR gene was flanked by multiple copies of mobile genetic elements. Comparative genomics analysis of a 9-kb transposon-like fragment of pKP18-125 showed that an approximately 2-kb sequence encoding lysR-floR-virD2 was conserved in the majority (79.01%, 83/105) of floR sequences collected from NCBI nucleotide database. Interestingly, the most similar sequence was a 7-kb fragment of plasmid pEC012 from an Escherichia coli strain isolated from a chicken. Conclusions: Identified on a transferable plasmid in the human pathogen K. pneumoniae, the floR gene may be disseminated through horizontal gene transfer from animal pathogens. Studies on the molecular mechanism of resistance gene dissemination in different bacterial species of animal origin could provide useful information for preventing or controlling the spread of resistance between animal and human pathogens.

Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate of Pantoea vagans PV989.

Pantoea vagans, a gram-negative bacterium from the genus Pantoea and family Enterobacteriaceae, is present in various natural environments and considered to be plant endophytes. We isolated the Pantoea vagans PV989 strain from the clinic and sequenced its whole genome. Besides a chromosome DNA molecule, it also harboured three large plasmids. A comparative genomics analysis was performed for the smallest plasmid, pPV989-94. It can be divided into four regions, including three conservative regions related to replication (R1), transfer conjugation (R2), and transfer leading (R3), and one variable region (R4). Further analysis showed that pPV989-94 is most similar to plasmids LA637P2 and pEA68 of Erwinia amylovora strains isolated from fruit trees. These three plasmids share three conservative regions (R1, R2, and R3). Interestingly, a fragment (R4') in R4, mediated by phage integrase and phage integrase family site-specific recombinase and encoding 9 genes related to glycometabolism, resistance, and DNA repair, was unique in pPV989-94. Homologues of R4' were found in other plasmids or chromosomes, suggesting that horizontal gene transfer (HGT) occurred among different bacteria of various species or genera. The acquired functional genes may play important roles in the adaptation of bacteria to different hosts or environmental conditions.

Clinical significance of plasma globotriaosylsphingosine levels in Chinese patients with Fabry disease.

Although plasma globotriaosylsphingosine (lyso-Gb3) is a promising biomarker of Fabry disease (FD), few studies have assessed the impact of lyso-Gb3 in patients with FD. A total of 38 patients diagnosed with FD at Ruijin Hospital between January 2012 and December 2014 were recruited in the current study. An additional 120 unrelated healthy individuals were selected as healthy controls. A simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed to determine lyso-Gb3 levels in plasma. Protein precipitation and glycolipid extraction were conducted using acetone/methanol. Clinical performance, including diagnostic value and disease surveillance, were compared between plasma lyso-Gb3 levels and α-galactosidase A (α-gal A) enzyme activity. The overall coefficient of variation values between inter- and intra-days varied between 2.8 and 18.9% and linearity correlation coefficients were ≥0.99 for all assays. Therefore, the effectiveness of the LC-MS/MS method was validated. Furthermore, a cut-off value of 0.81 ng/ml plasma lyso-Gb3 was able to separate patients with FD from healthy individuals. The sensitivity of this cut-off was 94.7% and the specificity was 100%. Compared with α-gal A enzyme activity, the diagnostic rate of patients assessed using plasma lyso-Gb3 levels was similar; however, there was a tighter correlation between plasma lyso-Gb3 levels and the mainz severity score index score in male patients (r=0.711 vs. r=-0.687). The sensitivity of plasma lyso-Gb3 in diagnosing female patients with FD was higher than α-gal A enzyme activity (82.4 vs. 23.5%). To the best of our knowledge, the present study is the first to report the effectiveness of plasma lyso-Gb3 levels in diagnosing Chinese patients with FD. Using α-gal A activity as a reference, the results of current study indicated that plasma lyso-Gb3 levels are more useful at diagnosing female patients with FD. Furthermore, plasma lyso-Gb3 levels are more suitable at determining overall disease severity in male patients.

Aberrant Humoral Immune Responses in Neurosyphilis: CXCL13/CXCR5 Play a Pivotal Role for B-Cell Recruitment to the Cerebrospinal Fluid.

Background: Previous studies documented that humoral immune responses participated in neurological damage in neurosyphilis patients. However, the mechanisms that trigger and maintain humoral immunity involved in neurosyphilis remain unknown. Methods: Using flow cytometry, expression of B cells was measured in neurosyphilis and non-neurosyphilis. Expression of immunoglobulin indices and chemokine ligand CXCL13 was detected by enzyme-linked immunosorbent assay. The migration and inhibition assays were evaluated by modified chamber assays. The presence of CXCL13+ cells, cluster of differentiation (CD)20+ B cells, CD3+ T cells, CD138+ plasma cells and CD35+ follicular dendritic cells was studied by immunohistochemistry. Results: Enrichment of B cells was observed and activated in the cerebrospinal fluid (CSF) of neurosyphilis patients. Immunoglobulin indices were increased and associated with the progress to neurosyphilis. High expression of CSF CXCL13 mediated B cell migration both in vitro and in vivo. There was a positive correlation among the CSF B cells, immunoglobulin indices, and CSF CXCL13 levels. Ectopic germinal centers (EGCs), important structures for humoral immunity, were observed in the intracranial syphilitic gumma. Conclusions: CXCL13/CXCR5 mediated the aggregation of B cells, that directed the aberrant humoral immune responses via the formation of EGCs, which suggests a molecular mechanism of neurological damage in neurosyphilis.

Comparative analysis of cluster versus conventional immunotherapy in patients with allergic rhinitis.

The present study aimed to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract administered in conventional and cluster immunotherapy regiments for patients with persistent allergic rhinitis. A total of 60 patients with moderate to severe allergic rhinitis caused by dust mites were treated for 1 year with either conventional immunotherapy (n=30) or cluster immunotherapy (n=30). Nasal conjunctival symptoms and signs were assessed to evaluate the clinical efficacy of the two regimens, and the incidence of local and systemic adverse reactions were also evaluated. The findings demonstrated that the cluster regimen reduced the duration between the initial and maintenance dose by >60%, and resulted in a significant improvement, as compared with the conventional regimen, after 6 weeks of observation (P<0.05). However, the incidence of local and systemic adverse reactions in the cluster regimen during the dose accumulation phase and the dose maintenance phase was not significantly different, as compared with the conventional immunotherapy regimen. These results suggest that cluster immunotherapy is efficacious and safe to treat patients who are clinically sensitive to dust mites.