A pediatric case of generalized lichen aureus.

Lichen aureus is a particularly rare subtype of pigmented purpuric dermatosis and is characterized by the sudden appearance of golden or rust-colored macules or needle-tip-sized flat papules (concentrated in one region to form lichenoid papules) on the lower limbs. These skin lesions are usually confined to an isolated, unilateral distribution, and linear segmental distribution is rare. In this report, we have documented one such case, where the lesions on the limb were arranged in strips (segmental distribution) that roughly followed the direction of the venous drainage. And the first attack and subsequent aggravation were both associated with the onset of allergic rhinitis, a Type I hypersensitivity.

Novel Pattern Recognition Receptor Protects Shrimp by Preventing Bacterial Colonization and Promoting Phagocytosis.

The recognition of pathogen-associated molecular patterns is accomplished by the recognition modules of pattern recognition receptors (PRRs). Leucine-rich repeats (LRRs) and C-type lectin-like domain (CTLD) represent the two most universal categories of recognition modules. In the current study, we identified a novel soluble and bacteria-inducible PRR comprising LRRs and a CTLD from the hepatopancreas of kuruma shrimp Marsupenaeus japonicus and named it Leulectin. The module arrangement of Leulectin is unique among all organisms. Both modules, together with the whole molecule, protected shrimp against Vibrio infection. By screening the pathogen-associated molecular patterns that shrimp might encounter, Leulectin was found to sense Vibrio flagellin through the LRRs and to recognize LPS through CTLD. The LRR-flagellin interaction was confirmed by pull-down and far-Western assays and was found to rely on the fourth LRR of Leulectin and the N terminus of flagellin. The recognition of LPS was determined by the long loop region of CTLD in a calcium-independent manner. By sensing the flagellin, LRRs could prevent its attachment to shrimp cells, thereby inhibiting Vibrio colonization. With the ability to recognize LPS, CTLD could agglutinate the bacteria and promote hemocytic phagocytosis. Our study clearly showed the division of labor and the synergy between different recognition modules and provided new insights into the concept of pattern recognition and the function of soluble PRRs in the antibacterial response.

Identification of a crustacean ß-1,3-glucanase related protein as a pattern recognition protein in antibacterial response.

Prophenoloxidase (proPO) activating system is an important immune response for arthropods. ß-1, 3-glucanase related protein (previously named as lipopolysaccharide and ß-1, 3-glucan binding protein (LGBP) in crustaceans) is a typical pattern recognition receptor family involved in the proPO activation by recognizing the invading microbes. In this study, we pay special attention to a bacteria-induced ß-1,3-glucanase related protein from red swamp crayfish Procambarus clarkii, an important aquaculture specie in China. This protein, designated PcBGRP, was found a typical member of crustacean BGRP family with the glucanase-related domain and the characteristic motifs. PcBGRP was expressed in hemcoyes and hepatopancreas, and its expression could be induced by the carbohydrate and bacteria stimulants. The induction by lipopolysaccharide (LPS) and ß-1,3-glucan (ßG) was more significant than by peptidoglycan (PG). The response of PcBGRP to the native Gram-negative bacterial pathogen Aeromonas hydrophila was more obvious than to Gram-positive bacteria. Using RNA interference and recombinant protein, PcBGRP was found to protect crayfish from A. hydrophila infection revealed by the survival test and morphological analysis. A mechanism study found PcBGRP could bind LPS and ßG in a dose-dependent manner, and the LPS recognizing ability determined the Gram-negative bacterium binding activity of PcBGRP. PcBGRP was found to enhance the PO activation both in vitro and in vivo, and the protective role was related to the PO activating ability of PcBGRP. This study emphasized the role of BGRP family in crustacean immune response, and provided new insight to the immunity of red swamp crayfish which suffered serious disease during the aquaculture in China.

Collaboration between a soluble C-type lectin and calreticulin facilitates white spot syndrome virus infection in shrimp.

White spot syndrome virus (WSSV) mainly infects crustaceans through the digestive tract. Whether C-type lectins (CLs), which are important receptors for many viruses, participate in WSSV infection in the shrimp stomach remains unknown. In this study, we orally infected kuruma shrimp Marsupenaeus japonicus to model the natural transmission of WSSV and identified a CL (designated as M. japonicus stomach virus-associated CL [MjsvCL]) that was significantly induced by virus infection in the stomach. Knockdown of MjsvCL expression by RNA interference suppressed the virus replication, whereas exogenous MjsvCL enhanced it. Further analysis by GST pull-down and coimmunoprecipitation showed that MjsvCL could bind to viral protein 28, the most abundant and functionally relevant envelope protein of WSSV. Furthermore, cell-surface calreticulin was identified as a receptor of MjsvCL, and the interaction between these proteins was a determinant for the viral infection-promoting activity of MjsvCL. The MjsvCL-calreticulin pathway facilitated virus entry likely in a cholesterol-dependent manner. This study provides insights into a mechanism by which soluble CLs capture and present virions to the cell-surface receptor to facilitate viral infection.

[Knock-down of ERα36 impacts the expression of differentiation protein in PC12 cells].

ERα36 is a novel subtype of estrogen receptor alpha (ERα) known to play an important role in breast cancer development and widely expressed in normal tissues and cells including nerve cells. However, the expression and function of ERα36 in nerve cells have not been well elucidated. To examine whether ERα36 is involved in differentiation of nerve cells, the differentiated and undifferentiated PC12 (PC12D and PC12unD) cells were used. Transfection of ERα36-shRNA plasmid into PC12 cells was performed to establish the ERα36 gene knock-down cells model. Immunocytofluorescence and Western blot were used to analyze the expression of Nestin, ß-tubulinIII and Neu-N in the PC12 cells. The results showed that ERα36 was expressed in both cell types. Compared with PC12D cells, PC12unD cells showed higher expression of Nestin and lower expression of ß-tubulinIII. ERα36-shRNA-mediated knock-down of ERα36 expression enhanced the expression of ß-tubulinIII and Neu-N, but attenuated Nestin expressions in PC12unD cells; ERα36 knock-down in PC12D cells mediated Nestin, ß-tubulinIII and Neu-N in a contrary manner. These results indicate that ERα36 knock-down appear to be associated with inhibiting differentiation in differentiated cells and promoting differentiation in undifferentiated cells, suggesting that ERα36 is a dual regulator in nerve differentiation.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.

Chinese medicine for idiopathic Parkinson's disease: A meta analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of Chinese medicine (CM) adjunct to conventional medications for idiopathic Parkinson's disease (PD). METHODS: Electronic English and Chinese databases including PubMed, Cochrane Library, Web of Science, Chinese Medical Current Contents, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Med Database, and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy. The extracted data was analyzed by the Review Manager 5.0. RESULTS: Twelve trials involving 869 participants were included in the meta-analysis. Unified PD Rating Scale (UPDRS) I, II, III, IV scores and UPDRS V-IV total scores were used to be the primary outcomes, Parkinson Disease Question-39 (PDQ-39) and Scores of Chinese Medical Symptoms were the secondary outcomes. CM adjunct therapy had greater improvement in UPDRS I [2 trials; standardized mean difference (SMD)-0.40, 95% confidence interval (CI)-0.71 to-0.09; Z=2.49 (P=0.01)], II [5 trials; SMD-0.47, 95% CI-0.69 to-0.25; Z=4.20 (P<0.01)], III [5 trials; SMD-0.35, 95% CI-0.57 to-0.13; Z=3.16 (P=0.002)], IV scores [3 trials; SMD-0.32, 95% CI-0.60 to-0.03; Z=2.17 (P=0.03)], UPDRS I-IV total scores [7 trials; SMD-0.36, 95%CI-0.53 to-0.20; Z=4.24 (P<0.05)]. PDQ-39 and Chinese medical symptoms compared to the conventional medication only. CONCLUSION: CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.

Phylogenetic analysis of basic helix-loop-helix transcription factors in the genome of a typical human-disease vector.

Ixodes scapularis, the black-legged tick, is one of the most common human-disease vectors and transmits Borrelia species, such as B. burgdorferi, as well as Theileria microti, Anaplasma phagocytophilum, etc. As basic helix-loop-helix (bHLH) transcription factors have been recognized for many years as important regulators of various developmental processes, we performed phylogenetic analysis of the black-legged tick genome in order to identify the number and family of bHLH transcription factors. Because bHLH family members have been identified in many organisms, including silkworm and fruit fly, we were able to conduct this survey and identify 58 putative bHLH transcription factors. Phylogenetic analysis revealed that the black-legged tick has 26, 10, 9, 1, 9, and 1 member in groups A, B, C, D, E, and F, respectively, whereas two were orphan genes. This analysis also revealed that unlike silkworm and fruit fly, the black-legged tick has no Mesp, Mlx, or TF4 family members, but has one more MyoRb family member. The present study provides useful background information for future studies of the black-legged tick as a disease vector with the goal of prevention and treatment.

Scavenger receptor B protects shrimp from bacteria by enhancing phagocytosis and regulating expression of antimicrobial peptides.

Scavenger receptors (SRs) are involved in innate immunity through recognizing pathogen-associated molecular patterns (PAMPs) and in pathogenesis of diseases through interactions with damage-associated molecular patterns (DAMPs). The roles of SRs in invertebrate innate immunity still need to be elucidated. Here we identify a class B scavenger receptor from kuruma shrimp, Marsupenaeus japonicus, designated MjSR-B1. The recombinant MjSR-B1 agglutinated bacteria in a calcium dependent manner and bound lipopolysaccharide and lipoteichoic acid. After knockdown of MjSR-B1, both the bacterial clearance and phagocytotic ability of M. japonicus against V. anguillarum and S. aureus were impaired, and several phagocytosis related genes were downregulated. The expression levels of antimicrobial peptides were also downregulated. Overexpression of MjSR-B1 led to enhanced bacterial clearance, phagocytosis rate and upregulation of phagocytosis-related and antimicrobial peptide genes. However, overexpression of mutant MjSR-B1ΔC, which lacks the carboxyl tail of MjSR-B1, had none of these effects. Our results indicate that MjSR-B1 can protect shrimp from bacteria by promoting phagocytosis and by enhancing the expression of antimicrobial peptides.

Two novel C-type lectins with a low-density lipoprotein receptor class A domain have antiviral function in the shrimp Marsupenaeus japonicus.

C-type lectins (CTLs) are pattern-recognition receptors (PRRs) that play important roles in immune response. In this study, two new CTLs containing a low-density lipoprotein receptor class A domain (LDLR) and a carbohydrate recognition domain (CRD) were identified in Marsupenaeus japonicus and designated as LdlrLec1 and LdlrLec2. The two CTLs expressed in all the tested tissues of shrimp, however, LdlrLec1 was mainly expressed in hemocytes, heart, gill and intestines, whereas LdlrLec2 was expressed in hepatopancreas and heart. The expression patterns of both LdlrLec1 and LdlrLec2 mRNA were obviously upregulated upon white spot syndrome virus (WSSV) challenge. Injection of recombinant LdlrLec1 or LdlrLec2 into shrimp inhibited WSSV replication, whereas knocking down the expression of LdlrLec1 and LdlrLec2 by RNA interference increased WSSV replication in vivo. The infection rates of WSSV incubated with LdlrLecs were reduced significantly compared with the control group. The LdlrLec proteins could interact with VP28, a major envelope protein of WSSV, which is necessary for the attachment and penetration of WSSV into shrimp cells. These results indicate that LdlrLec1 and LdlrLec2 may function in antiviral response by binding to WSSV and inhibiting their pervasion and replication in shrimp.

Antibacterial activity of serine protease inhibitor 1 from kuruma shrimp Marsupenaeus japonicus.

Serine protease inhibitors (Serpins) are a large family of protease inhibitors involved in many critical biological processes such as blood coagulation, fibrinolysis, programmed cell death, development, and innate immunity. We identified MjSerp1, a serpin in the kuruma shrimp Marsupenaeus japonicus. The MjSerp1 cDNA has a 1239 bp open reading frame (ORF) that encodes a 412-amino acid protein with a 23 aa signal peptide and a classic serpin domain. MjSerp1 has a calculated molecular mass of 46.3 kDa and a predicted isoelectric point of 5.51. MjSerp1 is mainly expressed in the hepatopancreas and the intestines, and is moderately expressed in hemocytes. Expression pattern analysis indicated that MjSerp1 is upregulated in the hepatopancreas after Vibrio anguillarum challenge. rMjSerp1 inhibits three Gram-positive bacteria and two Gram-negative bacteria, but does not inhibit phenoloxidase activity. The microorganism binding assay showed that rMjSerp1 closely binds to both Gram-positive and Gram-negative bacteria. MjSerp1 also exhibits inhibitory activity against microbial serine proteases, such as subtilisin A and proteinase K, indicating that MjSerp1 acts as a microbial serine protease inhibitor. rMjSerp1 injection into shrimp enhances V. anguillarum clearance, but MjSerp1 knockdown through RNA interference impairs Vibrio clearance in vivo. These results indicate that MjSerp1 functions as a direct effector in the bacterial clearance of M. japonicus. All together, our findings provide novel evidences for the serine protease inhibitor in shrimp immunity.

Induction of Hyperalgesia in Pigs through Blocking Low Hydraulic Resistance Channels and Reduction of the Resistance through Acupuncture: A Mechanism of Action of Acupuncture.

According to the classic theory of Chinese medicine, pain is due to the blockage in meridian channels, and acupuncture was invented to treat pain by "dredging" the channels. To test the theory, a hyperalgesia model was made by injecting hydrogel into low hydraulic resistance channel (LHRC) in 12 anaesthetized minipigs. Tail-flick threshold and ear-flick threshold were measured using a thermal radiation dolorimeter, and relative flick threshold (RFT) was calculated. Hydraulic resistance (HR) was measured with a biological HR measuring instrument on low HR points on LHRC and on control points with higher HR located outside LHRC; readings were recorded before, during, and after acupuncture treatment. RFT decreased after blocking the LRHC and was still significantly decreased 2 days and 4 days afterwards. No significant changes occurred when injecting saline into the same points or injecting gel into points outside the channel. Subsequent acupuncture reduced HR on LRHC along meridians but had no significant effect on sites with higher HR located outside LHRC. One of the mechanisms of action of acupuncture treatment for chronic pain may be that acupuncture affects peripheral tissue by reducing the HR in LHRC along meridians, improving the flow of interstitial fluid and removing algogenic substances and thereby relieving pain.

[Influence of mechanical pressure on the change of acupuncture-induced transcutaneous CO2 emission].

OBJECTIVE: To investigate conduction of acupuncture effect and the influence of mechanical pressing meridians on it. METHODS: In twenty healthy volunteers (8 males and 12 females, aged 29 years on average), by using a Frewil Q. F. apparatus, transcutaneous CO2 emission (TCE) was measured before, during and after acupuncture at Neiguan (PC 6), respectively. The locations being measured were Quze (PC 3) and four points including two non-acupoints along the Pricardium Meridian (Point A and B) and two non-acupoints apart from the Pericardium Meridian (Point C and D). Point A was located at the lower one fourth of the line connecting Tianquan (PC 2) and Quze (PC 3), and Point B located at the middle of the line connecting Ximen (PC 4) and Quze (PC 3). Point C was located 2 cm lateral on the ulnar side to Point A, and Point D located 2 cm lateral on the ulnar side to Point B. The above results were compared with those obtained after mechanical pressure of 1 kg (area 1 cm X 2 cm) applied on Ximen (PC 4) and Daling (PC 7), respectively, to observe their effect on TCE. RESULTS: During and after acupuncture at Neiguan (PC 6) without mechanical pressure, TCE at Quze (PC 3), point A and B increased significantly (P < 0.05), but not at point C and D (P > 0.05). While applying mechanical pressure at Ximen (PC 4), no significant increase was found on the three points during and after acupuncture. When applying pressure at Daling (PC 7), significant increases of TCE were also found at Quze (PC 3) and point A during acupuncture (P < 0.05), and a significant increase of TCE was found at point B after acupuncture with pressure keeping (P < 0.05). CONCLUSION: Acupuncture can enhance energy metabolism along meridians, and this effect can be blocked by mechanical pressure.

[Some misunderstandings of deqi phenomenon: from historic review to experimental study].

In this paper, the authors trace back to the historic source of deqi and needling sensation, and probe the misunderstanding course of the feeling of sourness, numbness, distension, aching or heaviness used as synonym of deqi, and explore and introduce the modern significance and experimental studies of deqi. Although there are arguments in relationship between the feeling of sourness, numbness, distension, aching or heaviness after acupuncture and effect of acupuncture at home and abroad, in fact, this is a misunderstanding of needling sensation replacing deqi. Sometimes acupuncture possibly does not induce sourness, numbness, distension, aching or heaviness, but it also induces patient's comfortable sensation and at the same time acupuncture practitioners possibly have a sensation under the hand, which is at the state of deqi. The two states will be detected by fMRI in experimental studies, so as to have indexes to be followed for deqi or needling sensation.

A discovery of low hydraulic resistance channel along meridians.

A hydro-mechanic model was put forward to study the fundamental nature of acupuncture meridians. The basic state of low hydraulic resistance was tested on humans and mini pigs using three methods. The first, a modified Guyton's method, proved that there was lower hydraulic resistance on meridians compared with nonmeridians. The second scanning method involved a single pressure transducer that can find the lowest resistance point in tissue, and the third method used two transducers and provided a more stable measurement. Using the latter method, low hydraulic resistance points were found very close to low impedance points along meridians. The transmission of artificial interstitial fluid pressure waves was measured to examine their connection to the low resistance points, with the result that a good connection between the points was confirmed. This means the points form channels along the meridians that we refer to as low hydraulic resistance channels. The channel was imaged through isotopic tracing and a migration of isotope (99m)Te could be found along the channel. The layer of the channel was detected by injecting Alcian blue and the track was found beneath the skin. All of the above experiments suggest the existence of a new type of channel in living tissues that has not yet been described in modern science, but coincides quite well with the Qi channel theory of traditional Chinese medicine.

[Experimental verification of "treating lumbar-back problems by puncturing Weizhong (BL 40)" with blood perfusion imaging technique].

OBJECTIVE: To verify the classic saying of "Treating lumbar-back problems by puncturing Weizhong (BL 40)" in acu-moxibustion learning and to explore its underlying mechanism. METHODS: Forty volunteer sublects were asked to accept twice tests respectively, i.e., acupuncture of Weizhong (BL 40) and Yanglingquan (GB 34), for observing changes of skin blood perfusion (SBP) at the low back part of the body by using a laser Doppler perfusion imager. The whole observed area (lower back) was divided into five sub-areas, left and right areas involving Line-one and Line-two of the Bladder Meridian. RESULTS: In comparison with pre-acupuncture, SBP of both BL40 and GB34 groups increased significantly from 4 minutes' retention of needles on to 12 mm after withdrawing acupuncture needle (P < 0.01), but no significant difference was found between two groups in SBP (P > 0.05). The change rates of SBP at Line-one and Line-two of the Bladder Meridian on the same side of the stimulated Weizhong (BL 40) were significantly higher than those of Yanglingquan (GB 34) (P < 0.05), but no significant changes were found on the opposite side (both Line-one and Line-two) of the Bladder Meridian. CONCLUSION: Acupuncture of both BL4O and GB34 can increase SBP at the low back of the body (involving the Bladder Meridian) on the same side, but the changing rate of SBP of BL4O is hiaher than that of GB34.