Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor-interacting protein kinase 3 -related signalling pathway.

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METH-induced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. The receptor-interacting protein kinase 3 (RIP3) was highly expressed in the neurons of human and mice exposed to METH, and RIP3-silenced or RIP1-inhibited protected neurons developed neuronal programmed necrosis in vitro and in vivo following METH exposure. Moreover, the RIP1-RIP3 complex causes cell programmed necrosis by regulating mixed lineage kinase domain-like protein (MLKL)-mediated cell membrane rupture and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Together, these data indicate that RIP3 plays an indispensable role in the mechanism of METH-induced neuronal programmed necrosis, which may represent a potential therapeutic target for METH-induced neurotoxicity.

Detection of Exogenous γ-Hydroxybutyric Acid in Rat Blood Exosomes.

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS: GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

Tp0136 targets fibronectin (RGD)/Integrin ß1 interactions promoting human microvascular endothelial cell migration.

Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed to analyze the role of Tp0136 in the migration of human microvascular endothelial (HMEC-1) cells and to explore the related mechanism. First, Tp0136 significantly promoted HMEC-1 cell migration. Furthermore, the levels of C-C motif ligand 2 (CCL2) mRNA and protein expression rose with the concentration and time increasing of Tp0136. The migration of HMEC-1 cells was significantly suppressed by an anti-CCL2 antibody and a CCR2 (the CCL2 receptor) inhibitor. Further study revealed that, in cells pretreated with anti-fibronectin antibody, anti-integrin ß1 antibody or RGD (Arg-Gly-Asp), the expression levels of CCL2 induced by Tp0136 were notably decreased. Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin ß1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin ß1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.

Recombinant Treponema pallidum protein Tp47 promotes the migration and adherence of THP-1 cells to human dermal vascular smooth muscle cells by inducing MCP-1 and ICAM-1 expression.

Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients.

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1ß production.

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Assessing effects of different processing procedures on the yield of Treponema pallidum DNA from blood.

In this work, we employed real-time PCR analysis targeting tp0574 to investigate the effects of different processing procedures on the yield of T. pallidum DNA from blood to improve assay sensitivity. The T. pallidum DNA yields following red blood cell lysis pretreatment were 40.4 times greater from whole blood and 32.4 times greater from residual hematocytes than yields without pretreatment. For the simulated whole-blood experiments, the T. pallidum DNA yields from the lower layer were 2.8, 4.6, 7.3, 12.6, 15.24, 16.7, 65.1 and 73.1 times those from the upper layer following centrifugation at 500×, 1000×, 2000×, 4000×, 5000×, 7000×, 10,000× and 20,000 × g, respectively. However, the T. pallidum DNA yields from blood clots were only 1.0% at different centrifugal forces. The experiment with infected rabbit blood showed results similar to those mentioned above. In addition, sample processing time (within 48 h) and storage temperature (4 °C and 25 °C) did not affect T. pallidum DNA extraction efficiency. The T. pallidum DNA yield can be significantly improved by red blood cell lysis pretreatment and appropriate centrifugation. Furthermore, the T. pallidum DNA extraction yield is greater from whole blood or residual hematocytes from anti-coagulated blood than from plasma, serum or blood clots.

Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-naïve patients: a case-control study in a Han Chinese population.

BACKGROUND: Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection. METHODS: During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level. RESULTS: We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480. CONCLUSIONS: TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease.

Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols.

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Epidemiological characteristics of respiratory viruses in children during the COVID-19 epidemic in Chengdu, China.

IMPORTANCE: During the coronavirus disease 2019 epidemic, the Chinese government launched and used a series of nonpharmaceutical interventions (NPIs), including banning social gatherings, wearing face masks, home isolation, and maintaining hand hygiene, to control the disease spread. Whether and how NPIs influence other respiratory viruses in children remain unclear. In this article, we analyzed relative data and found that the number of samples and positive proportion of respiratory viruses decreased significantly compared with that before the epidemic. Clinicians and public health policymakers should pay attention to changes in the epidemic trends and types of respiratory viruses and maintain monitoring of respiratory-related viruses to avoid possible abnormal rebounds and epidemic outbreaks of these viruses.

Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Tunable bandgap in silicene and germanene.

By using ab initio calculations, we predict that a vertical electric field is able to open a band gap in semimetallic single-layer buckled silicene and germanene. The sizes of the band gap in both silicene and germanene increase linearly with the electric field strength. Ab initio quantum transport simulation of a dual-gated silicene field effect transistor confirms that the vertical electric field opens a transport gap, and a significant switching effect by an applied gate voltage is also observed. Therefore, biased single-layer silicene and germanene can work effectively at room temperature as field effect transistors.

Lead poisoning in a 6-month-old infant: a case report.

Background: Lead is a toxic element of the environment that leads to major complications once it enters the blood stream, affecting multiple organs and systems of the body. Methods: We present a case of a 6-month-old female infant diagnosed with lead poisoning after presenting for routine child health care. The child's mother denied that the infant had a history of exposure to lead-containing substances. After a month of calcium supplementation, the patient's blood lead level remained elevated. We then tested the blood lead level of the mother and father. The results showed that the blood lead level of the mother was 77.0 µg/L and that of the father was 36.9 µg/L. The high blood lead level of the mother attracted our attention. We found that the mother had been using an external traditional Chinese medicine, Hu Wang Fen, which contains lead. After the mother's discontinuation of use of the traditional medicine, the child was treated with symptomatic treatment and chelation therapy. Subsequently, the patient's blood lead level decreased significantly. Results: Lead toxicity can be a life-threatening problem because of its potential for severe complications. In children, there is no safe blood lead level, and the toxic effects of lead can be prevented by the awareness and avoidance of traditional Chinese medicines that may contain lead. Conclusion: Even though the diagnosis of lead poisoning remains difficult in children, it must be taken into consideration by the clinician when treating a child using traditional Chinese medicines.

[Effects of paclitaxel on proliferation and transition of phenotype in platelet-derived growth factor-BB-induced pulmonary vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of paclitaxel on the phenotypic modulation induced by platelet-derived growth factor (PDGF-BB) in rat pulmonary vascular smooth muscle cells (PVSMC). METHODS: The proliferation of PVSMC isolated from SD rats cultured in vitro was induced by PDGF-BB and then intervened by different concentration of paclitaxel. MTT and [³H]-thymidine incorporation were used to detect the changes of cell proliferation. The expression level of alpha-smooth muscle-actin (SM-α-actin) and smooth muscle protein 22alpha (SM22α) were tested by Western blot. Confocal laser scanning microscopy was applied to observe the change of fluorescence intensity. RESULTS: Treatment with PDGF-BB for 24 hours results in a significant increase in [³H]-thymidine incorporation and marked change in phenotype and cytoskeleton, Paclitaxel inhibited the proliferation of PVSMC induced by PDGF-BB, the inhibition rate was 45.4%, 35.4%, 21.6% (P < 0.01) tested by[³H]-thymidine incorporation and 40.0%, 30.0%, 18.0% (P < 0.01) tested by MTT. Meanwhile, the paclitaxel promoted the expression level of SM-α-actin and SM22α. Fluorescence intensity of F-actin decreased significantly. CONCLUSION: Paclitaxel may play an important role in vascular remodeling by changing the phenotypes and cytoskeleton of VSMC stimulated by PDGF-BB.

Advances in laboratory diagnostic methods for cerebrospinal fluid testing for neurosyphilis.

Neurosyphilis is a chronic infectious disease caused by the invasion of Treponema pallidum into the central nervous system. In recent years, with the increase in the latent syphilis infection rate, the incidence of neurosyphilis has gradually increased, the typical symptoms of neurosyphilis have decreased, atypical manifestations have increased, and the clinical manifestations have become increasingly diverse. Cerebrospinal fluid testing plays an important role in the diagnosis of neurosyphilis. In recent years, there have been many advances in cerebrospinal fluid testing. This review focuses on the current and potential laboratory indicators of neurosyphilis in cerebrospinal fluid, aiming to provide a reference for clinical application and ideas for future experimental research of neurosyphilis.

Missed opportunities for screening congenital syphilis early during pregnancy: A case report and brief literature review.

Congenital syphilis is a significant public health problem. Pregnant women infected with Treponema pallidum present with various clinical manifestations, mainly including skin or visceral manifestations. The extensive clinical manifestations of T. pallidum infection mimic those of many other diseases during pregnancy, which may lead to delayed diagnosis and serious consequences. We report a case of fetal T. pallidum infection and premature delivery in a woman whose syphilis screening was negative at 16 weeks of gestation. Despite presenting to the dermatologist at 24 weeks of gestation with maculopapular rash which is usually associated with secondary syphilis, the diagnosis of syphilis was not considered. This case shows that even if early syphilis screening of pregnant women is negative, they may still get infected with T. pallidum later on in pregnancy. Therefore, in patients presenting with a rash without an obvious cause, T. pallidum infection should be excluded. The health status of patients' spouses should be assessed during pregnancy. Additionally, perinatal health education is necessary for women and their spouses during pregnancy. The abovementioned factors could reduce the probability of T. pallidum infection in pregnant women and their infants.

Structural, electronic and magnetic properties of ultra-narrow NbSe2 nanoribbons.

Structural, electronic and magnetic properties of ultra-narrow NbSe2 nanoribbons with different chirality and edge structures are studied by using density functional theory calculations. Armchair-like NbSe2 nanoribbons exhibit nonmagnetic and metal behavior. Zigzag-like NbSe2 nanoribbons always have ferromagnetic ground states with electronic types ranging from semiconductor, metal, even to half-metal. And stability estimation indicates that the zigzag-like NbSe2 nanoribbons with 50% Se passivation at Nb edges are the most energetically stable. All these findings suggest potential applications of NbSe2 nanoribbons in spintronic devices.

Pathological methamphetamine exposure triggers the accumulation of neuropathic protein amyloid-ß by inhibiting UCHL1.

Methamphetamine (METH), a powerful psychoactive drug, causes damage to the nervous system and leads to degenerative changes similar to Alzheimer's disease (AD), however, the molecular mechanism between the toxicity of METH and AD-related symptoms remains poorly understood. In this study, we investigated the effect of METH exposure on the accumulation of amyloid-ß by establishing the animal and cell models. The results showed that METH exposure increased amyloid precursor protein (APP) and ß-secretase (BACE1), contributed to the accumulation of amyloid-ß, and which was alleviated with the pretreatment of BACE1 inhibitor. In addition, METH exposure decreased ubiquitin carboxy-terminal hydrolases L1 (UCHL1) which was related to the degradation of BACE1, and therefore led to the up-regulation of BACE1. In summary, the study could provide a new insight into the molecular mechanisms of METH toxicity and new evidence for the link between METH abuse and AD.

Mixed low-dimensional nanomaterial: 2D ultranarrow MoS2 inorganic nanoribbons encapsulated in quasi-1D carbon nanotubes.

Quasi-one-dimensional nanotubes and two-dimensional nanoribbons are two fundamental forms of nanostructures, and integrating them into a novel mixed low-dimensional nanomaterial is fascinating and challenging. We have synthesized a stable mixed low-dimensional nanomaterial consisting of MoS(2) inorganic nanoribbons encapsulated in carbon nanotubes (which we call nanoburritos). This route can be extended to the synthesis of nanoburritos composed of other ultranarrow transition-metal chalcogenide nanoribbons and carbon nanotubes. The widths of previously synthesized MoS(2) ribbons are greater than 50 nm, while the encapsulated MoS(2) nanoribbons have uniform widths down to 1-4 nm and layer numbers down to 1-3, depending on the nanotube diameter. The edges of the MoS(2) nanoribbons have been identified as zigzag-shaped using both high-resolution transmission electron microscopy and density functional theory calculations.