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A rare case of neurosyphilis with oral condyloma lata and fingernail damage is reported. A 49-year-old male presented with a two-month history of copper-red macules on the palms of both hands and verrucous plaques on the tongue tip for 1 month, and dark shadows on the left eye for 1 week. Dermatological examination revealed uneven and partially thickened nail surfaces of the left thumb and right index finger. The palms were scattered with copper-red macules in the size of mung beans, surrounded by collar-like desquamation. Flat-topped verrucous plaques could be seen on the mucosa of the tongue tip. Hearing was slightly less in the left ear than in the right ear. Corrected visual acuity was 1.0 in the right eye and 0.8 in the left eye. Laboratory tests showed positive for both serum Treponema pallidum particle agglutination (TPPA) (>1∶1 280) and Tolulized red unheated serum test (TRUST) (1∶64). Moreover, the cerebrospinal fluid (CSF) was positive for TRUST(1∶1), TPPA(1∶640) and venereal disease research laboratory (VDRL) (1∶2). The presence of Treponema Pallidum (T. Pallium) in oral verrucous plaque was confirmed by metagenomics next-generation sequencing (mNGS) technology. The diagnosis was neurosyphilis, secondary syphilis (oral flat condyloma). After 2 weeks of treatment with aqua penicillin at a dose of 4 million U q4h, almost all clinical manifestations were improved. Serum TRUST titer was decreased to 1∶8 after 3 months. The follow-up is still ongoing.

Objective To report a case of hemophagocytic lymphohistiocytosis syndrome (HLH) secondary to systemic hydroa vacciniforme lymphoproliferative disorder (systemic HVLPD) and review relevant literature, in order to improve understanding of the disease. Methods Clinical data of the case, laboratory examination, histopathology, immunohistochemistry, TCR gene rearrangement, and whole exon gene sequencing were collected for analyses. Results A 19 years old man was admitted to the hospital due to generalized papules, blisters, necrotic scabs and fever for 7 months. The clinical manifestations included hydroa vacciniforme-like rashes, lymphadenopathy, splenomegaly, pancytopenia, hypertriglyceridemia, decreased NK cell activity, high levels of sIL-2r, positive for VCA-IgA and EA-IgA, and elevated EBV DNA load. The whole exon sequencing did not show pathogenic gene mutations. Histopathological changes in the skin lesions included liquefaction degeneration of epidermal and follicular basal cells, pigmentary incontinence, lymphocytic infiltrates of the epidermis and follicular epithelium, perivascular and perifollicular infiltrates of lymphocytes and eosinophils in the dermis, extravasation of erythrocytes, as well as focal infiltrates of atypical lymphoid cells around appendages and small blood vessels. Pathologic mitosis was visible. Immunohistochemistry showed CD3 (+), CD5 (+), CD20 (individual+), CD30 (small patch+), CD79a (individual+), CD4 (+), CD7 (+), CD8 (+), TIA-1 (+), CD56 (scattered lymphocyte+), ≈50% of Ki-67(+), and in situ hybridization EBER (+). TCRβ gene monoclonal rearrangements were detected. According to the results of clinical and auxiliary examination, patient was diagnosed with HLH secondary to systemic HVLPD. After 8 months of follow-up, the patient passed away while waiting for transplantation of allogeneic hematopoietic stem cells. Conclusions Systemic HVLPD is rare and requires vigilance for the development of secondary hemophagocytic syndrome. The awareness of hemophagocytic syndrome should be improved to avoid possible misdiagnosis and delayed treatment.

Fragile X mental retardation protein (FMRP) is a selective RNA-binding protein that is highly expressed in neurons and influences cytoskeletal remodeling, cell-cell signal transduction and interactions. Patients with fragile X syndrome display FMRP deficiency and a lower risk of cancers. However, the specific function of FMRP and the underlying mechanisms are not clear. Evidence indicates the involvements of FMRP in multiple processes of malignant development, including tumor cell migration, invasion, apoptosis, proliferation and metastasis. In addition, FMRP is associated with the occurrence, development and prognosis of tumors. In this paper, we review the progress on the role of FMRP in the pathogenesis of tumors, exploring more potential biomarkers of tumors and new therapeutic targets.

Objective To investigate the expression of fragile X mental retardation protein (FMRP) in Chinese patients with malignant melanoma and its correlation with hematologic ratios. Methods Lesional skin samples were collected from 23 Chinese with malignant melanoma (melanoma group), and skin samples from 10 normal subjects served as controls (normal skin group). The expression of FMRP was observed using immunohistochemical(IHC) staining, and two scoring methods (H-Score and IRS) were used to evaluate the expression levels. The relationship between FMRP and different pathological grades and stages of malignant melanoma was assessed. The association of FMRP with some hematological ratios, such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and systemic inflammatory markers (SIM) in patients with malignant melanoma were analyzed. Results The expression levels of FMRP in the melanoma were significantly higher than that in the normal skin (P0.05). Expression levels of FMRP were positively correlated with NLR and SIM, while negatively correlated with LMR. Conclusions FMRP is highly expressed in cutaneous malignant melanoma and its expression levels are significantly correlated with NLR, SIM, and LMR.

Objective To investigate the clinical utility of identifying circulating tumor cells (CTC) and circulating tumorigenic endothelial cells (CTEC) in skin malignancies. Methods Subtraction enrichment-immunostaining and fluorescence in situ hybridization (SE-iFISH) were used to detect the number of CTC and CTEC in the peripheral blood of 5 patients with skin tumor (tumor group) and 14 healthy individuals (healthy controls), and the detection rate was calculated. The subtype characteristics of CTC/CTEC and the correlation between the number of CTC/CTEC and the clinical characteristics of the patients were analyzed. Results The positive rates of CTC and CTEC in the tumor group were 100%. The average CTC were (6.93±8.18) /mL and CTEC were (1.60±1.03) /mL in the peripheral blood of the tumor group. The positive rates of CTC and CTEC in the healthy controls were both 64%. The average CTC were (0.19±0.21) /mL, and CTEC were (0.30±0.33) /mL in the peripheral blood of the healthy controls. Patients with larger diameter of tumor, lymph node metastasis, and clinical stages of III and IV had higher levels of CTC and CTEC; Large CTC accounted for 88.46% (184/208) of the total tumor cells, while large CTEC accounted for 81.25% (39/48) of the total tumor cells, which mainly were ≥ pentaploid CTC and CTEC. Conclusions Using SE-iFISH, the detection rates of CTC/CTEC are high in patients with skin tumors. The amounts of CTC and CTEC are correlated with the clinical features of patients. A higher proportion of CTC and CTEC is large multiploid cells in peripheral blood of subjects with skin tumors.

A case of trichilemmal cysts is reported. A 31-year-old man presented with a 5-year history of nodule on his back with enlargement, pain and itching for 1 month. Dermatological examination showed erythema and erythematous plaques scattered on the trunk and extremities, covered with a small amount of silvery white scales. A demarcated exophytic tumor sized 2 cm×3 cm in dark red color was seen on the back, with telangiectasia on the surface. The tumor was slightly soft and tenderness (+) with poor mobility. No erosion or ulceration was observed. Histopathological examination showed a dermal cyst, which wall was composed of stratified squamous cells, and the content of cyst was keratin with focal calcification. The patient was diagnosed with trichilemmal cyst. Complete resection was given. No recurrence was observed over 4 months of follow-up.

Objective To investigate the effects of β-estradiol (E2) on the phosphorylation of JAK/STAT, PI3K/AKT signaling pathways and the expression of IL-17A in mouse spleen mononuclear cells treated with IL-36β. Methods The spleens were isolated from female SPF C57BL/6 mice aged 6-8 weeks. The mononuclear cell suspensions were obtained from spleens by density gradient centrifugation. The suspensions of mononuclear cells were transferred into four petri dishes, with 1.5×107 cells/dish, followed by the treatment with either E2 (10-8 mol/L) or IL-36β (10 ng/mL) or IL-36β+E2, while untreated cells served as normal controls. Western blotting was used to assess the changes in phosphorylation of JAK/STAT and PI3K/AKT proteins 30 min after incubation with IL-36β or E2. Moreover, the mononuclear cells were also treated with IL-36β, E2, JAK inhibitor and PI3K inhibitor, respectively, followed by assessment of IL-17A mRNA levels at 6, 12 and 24 h, meanwhile expression levels of IL-17A protein were measured with Western blot at 24 h. Results IL-36β activated the phosphorylation of JAK3/STAT2 and PI3K/AKT in mouse spleen mononuclear cells, while E2 inhibited such activation induced by IL-36β. Expression levels of IL-17A mRNA differed significantly among four groups of cells at 6, 12 and 24 h (F=25.50, 127.04 and 9.76, respectively, all P

Objective To explore the effect of Treponema pallidum (Tp) -induced exosomes (EXOTp) by macrophages on macrophage polarization. Methods Human monocyte-macrophages (THP-1) were induced into macrophages, followed by stimulation with or without Tp for 24 h. After changing medium, cells were cultured for additional 48 h. The macrophage exosome suspension was collected, and exosomes were isolated by differential speed centrifugation. Isolated exosomes were identified by both Western blotting and transmission electron microscopy, and were quantitated with nanoparticle tracking technology. The internalization of the macrophages in the two groups was observed under a laser confocal microscope. In the experimental group, the isolated EXOTp was incubated with M0 macrophages for 24 h. Incubation of M0 macrophages with exosomes produced by non-Tp-treated macrophages served as negative controls, while M0 macrophages incubated without exosomes served as blank controls. At 6,12, and 24 h, the expression levels of INOS, IL-12, Arg-1, IL-10 and other mRNAs in all three groups were detected by qRT-PCR. Flow cytometry was used to identify macrophage phenotypes using MHC-Ⅱ, CD86, CD206, and CD209 markers. Results qRT-PCR showed that the expression levels of INOS and IL-12 mRNA in experimental group were time-dependently up-regulated (P0.05). Flow cytometry results showed that MHC-Ⅱ was positive (P0.05). Conclusions The exosomes secreted by THP-1-derived macrophages cannot induce the polarization of M0 macrophages to M1 macrophages. Upon the stimulation with Tp, the exosomes secreted by THP-1-derived macrophages can induce polarization of M0 macrophages to M1 macrophages.

MiRNA is a class of non-coding RNAs with regulatory functions that regulate gene expression after transcription. In recent years, more and more evidence has shown that pathogens regulate the expression of relevant inflammatory factors though miRNA in infection diseases which can affect the occurrence, development and outcome of the disease. However regulatory mechanism is unclear. Therefore, we review the research advance of miRNA in inflammatory response of infectious diseases.

Netherton syndrome (NS) is a rare recessive syndromic ichthyosis due to mutations in the SPINK5 gene characterized by a triad of congenital ichthyosiform erythroderma (CIE) and/or ichthyosis linearis circumflexa (ILC), hair shaft abnormalities, and elevated IgE levels. However, NS patients often suffer from misdiagnosis, delayed treatment, or even ineffective therapy for the triad is not always complete. To achieve identification early and intervention effectively, the paper comprehensively reviewed the pathogenesis progression, clinical features, histopathology and immunohistochemistry, diagnosis and differential diagnosis, and treatment advancement of the NS.

Objective To explore the diagnostic value of different subtypes of Treponema pallidum (Tp) adhesin protein TP0136 in the blood of neurosyphilitic patients. Methods The general conditions were compared in syphilitic patients with vs. without neuroinvolvement. Molecular cloning technique was used to express and purify Nichols Seattle TP0136 (abbreviated as NST) and Nichols Houston TP0136 (abbreviated as NHT) recombinant proteins. ELISA assay was used to measure serum levels of NST and NHT antibodies in neurosyphilitic and non-neurosyphilitic patients. Results There were no significant differences in age, gender, geographic region and occupation between neurosyphilitic and non-neurosyphilitic patients (P>0.05), while marital status, neurological symptoms, serum or plasma TRUST and TPPA titer, serum or plasma TP-IgM positive rate, cerebrospinal fluid TRUST and TPPA titer differed significantly (P