Duality of immune recognition by tomato and virulence activity of the Ralstonia solanacearum exo-polygalacturonase PehC.

Ralstonia solanacearum is a devastating soil-borne bacterial pathogen capable of infecting many plant species, including tomato (Solanum lycopersicum). However, the perception of Ralstonia by the tomato immune system and the pathogen's counter-defense strategy remain largely unknown. Here, we show that PehC, a specific exo-polygalacturonase secreted by Ralstonia, acts as an elicitor that triggers typical immune responses in tomato and other Solanaceous plants. The elicitor activity of PehC depends on its N-terminal epitope, and not on its polygalacturonase activity. The recognition of PehC specifically occurs in tomato roots and relies on unknown receptor-like kinase(s). Moreover, PehC hydrolyzes plant pectin-derived oligogalacturonic acids (OGs), a type of damage-associated molecular pattern (DAMP), which leads to the release of galacturonic acid (GalA), thereby dampening DAMP-triggered immunity (DTI). Ralstonia depends on PehC for its growth and early infection and can utilize GalA as a carbon source in the xylem. Our findings demonstrate the specialized and dual functions of Ralstonia PehC, which enhance virulence by degrading DAMPs to evade DTI and produce nutrients, a strategy used by pathogens to attenuate plant immunity. Solanaceous plants have evolved to recognize PehC and induce immune responses, which highlights the significance of PehC. Overall, this study provides insight into the arms race between plants and pathogens.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Epithelial Cell NOD1/IRGM Recruits STX17 to Neisseria gonorrhoeae-Containing Endosomes to Initiate Lysosomal Degradation.

Neisseria gonorrhoeae establishes tight interactions with mucosal epithelia through activity of its type IV pilus, while pilus retraction forces activate autophagic responses toward invading gonococci. Here we studied pilus-independent epithelial cell responses and showed that pilus-negative gonococci residing in early and late endosomes are detected and targeted by nucleotide-binding oligomerization domain 1 (NOD1). NOD1 subsequently forms a complex with immunity-related guanosine triphosphatase M (IRGM) and autophagy-related 16-like 1 (ATG16L1) to activate autophagy and recruit microtubule-associated protein light chain 3 (LC3) to the intracellular bacteria. IRGM furthermore directly recruits syntaxin 17 (STX17), which is able to form tethering complexes with the lysosome. Importantly, IRGM-STX17 interactions are enhanced by LC3 but were still observed at lower levels in an LC3 knockout cell line. These findings demonstrate key roles for NOD1 and IRGM in the sensing of intracellular N gonorrhoeae and subsequent directing of the bacterium to the lysosome for degradation.

Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

Bartonella Prevalence and Genome Sequences in Rodents in Some Regions of Xinjiang, China.

In this study, we investigated Bartonella infection and its genetic diversity in rodents in Beitun, Xinjiang Uygur Autonomous Region, China. Small mammals were captured using snap traps at four sampling sites in 2018. Spleen and liver tissues were collected and cultured to isolate Bartonella strains. Whole-genome sequencing was performed on the strains identified as Bartonella by gltA gene PCR, and the average nucleotide identity (ANI) of the genomes was calculated by using FastANI v1.33. Phylogenetic trees were constructed for the samples positive for Bartonella spp. by the gltA PCR assay based on 1,290-bp gltA genes, 2,903-bp rpoB genes, and core-genome single nucleotide polymorphisms (SNPs). Among 66 rodents, 11 were positive for Bartonella, with an infection rate of 16.67%. The rodent infection rates in different tissues (χ2 = 2.133; P = 0.242), species (χ2 = 9.631; P = 0.141), and habitats (χ2 = 4.309; P = 0.312) did not show statistical differences. Bartonella spp. isolated from the rodents were phylogenetically divided into six clades (two different Bartonella species were detected in two rodents). By comparing phylogenetic trees based on gltA genes, rpoB genes, and SNPs, we found that the topological structures of several evolutionary trees are different. However, the Bartonella strains isolated in this study were clustered into six clusters in different phylogenetic trees. Broad distributions and high genetic diversity of Bartonella strains were observed among rodents in Beitun, Xinjiang. IMPORTANCE Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. Xinjiang is one of the provinces with the most abundant species of Bartonella in China, but there are few reports about the prevalence of Bartonella in the Beitun area. This research aims to investigate the occurrence and prevalence of Bartonella infection in rodents at these sampling sites and provide a basis for the prevention and control of rodent Bartonella species in Beitun and the surrounding areas of Xinjiang.

No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors.

BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.

Impacts of exposure to topical calcineurin inhibitors on metabolism in vitiligo infants.

BACKGROUND: Tacrolimus ointment is a recently developed topical immunomodulator that has been approved for use in patients with vitiligo older than 2 years. Concern regarding potential systemic toxic effects has limited treatment options for children younger than 2 years. We wanted to determine whether topical tacrolimus therapy is safe and effective in patients with vitiligo younger than 2 years. METHODS: The present 6-month clinical trial was conducted to evaluate the efficacy and safety of 0.03% tacrolimus in the treatment of vitiligo in children under 2 years of age. Meanwhile, serum and urine samples were collected, and liquid chromatography-mass spectrometry was performed to generate the serum and urine metabolic profile data of patients and healthy controls. RESULTS: The overall response rate at the sixth month, which was defined by the degree of re-pigmentation, was 100%. As revealed by blood monitoring and metabolite detection 6 months later, there was no difference between the treatment group and the control group. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. CONCLUSIONS: Tacrolimus ointment appears to be effective and safe in the treatment of vitiligo in children younger than 2 year. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR 2100045920. IMPACT: We first reported the efficacy and safety of topical application of 0.03% tacrolimus ointment in infants with vitiligo characterized by the metabolites. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. This study provide evidence for the TCI treatment of infants with vitiligo.

Diet, physical activity, and obesity among ART-experienced people with HIV in South Africa.

The prevalence of non-communicable diseases (NCDs) is increasing in South Africa, in part due to poor nutrition, physical inactivity, and obesity. We characterized the habits and understanding of diet, exercise, and obesity among people with HIV (PWH) taking antiretroviral therapy (ART). We conducted a cross-sectional study of ART-experienced PWH attending an HIV community health center near Cape Town, South Africa. We included PWH currently prescribed ART, older than 21y, and not pregnant. We collected demographic and clinical information and interviewed participants regarding their behaviors and knowledge related to diet, physical activity, and obesity. From March 2015 - February 2016, we enrolled 458 participants. Self-reported diets were low in nutritional diversity: 202 reported eating only starch and protein without vegetable/fruit in the prior 24 h. Although most participants (96%) acknowledged that exercise had health benefits, only 215 participants engaged in daily 30-minute walking or exercise. One quarter of participants recognized nocontributors to obesity, and almost 20% identified no health problems associated with obesity. Participants had diets low in nutritional diversity, modest exercise habits, and limited understanding of the impact of obesity on health. Further understanding of barriers to improving diet and exercise and reducing obesity are essential, especially as PWH age.

[Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD].

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1ß (IL-1ß), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1ß, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

[Hemophagocytic Syndrome Secondary to Human Parvovirus B19 Infection in an Acquired Immunodeficiency Syndrome Patient:Report of One Case].

The acquired immunodeficiency syndrome patients with compromised immunity are prone to hemophagocytic syndrome secondary to opportunistic infections.This paper reports a rare case of hemophagocytic syndrome secondary to human parvovirus B19 infection in an acquired immunodeficiency syndrome patient,and analyzes the clinical characteristics,aiming to improve the diagnosis and treatment of the disease and prevent missed diagnosis and misdiagnosis.

Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease.

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.

Moenomycin is broadly active against multidrug-resistant Neisseria gonorrhoeae and clears an infection from a murine vaginal tract infection model.

OBJECTIVES: Ceftriaxone therapy for gonorrhoea has become under increasing pressure due to waning susceptibility levels and emergence of high-level resistant strains such as the FC428 clone. Moenomycin was recently identified to display potent anti-gonococcal activity against some reference strains. Therefore, the aim of this study was to investigate moenomycin in vitro and in vivo antimicrobial activity. METHODS: Moenomycin in vitro antimicrobial activity was investigated against 575 clinical isolates, including strains associated with the FC428 clone, using the agar dilution method. Moenomycin in vivo activity was investigated in a mouse vaginal tract gonococcal infection model. RESULTS: The moenomycin MIC range for the strain collection was 0.004-0.06 mg/L, with a MIC50 of 0.016 mg/L and a MIC90 of 0.03 mg/L. The correlation between moenomycin and ceftriaxone susceptibility levels was poor (R = 0.13), while the fractional inhibitory concentration index (FICI) resulted in indifference for all tested strains. Therefore, development of cross-resistance between moenomycin and ceftriaxone is unlikely for N. gonorrhoeae. Determination of the moenomycin mode of activity against N. gonorrhoeae by time-kill assays showed that moenomycin is bactericidal, with over 104-fold inactivation observed after 4 h exposure. Finally, an intramuscular moenomycin dose of 10 mg/kg given on 2 consecutive days was able to clear a gonococcal infection in a mouse vaginal tract infection model within 1-3 days after the second dose, which was significantly faster than for mice treated with the vehicle control (P < 0.0001). CONCLUSIONS: Moenomycin displays potent in vitro and in vivo antimicrobial activity against N. gonorrhoeae, warranting further exploration as alternative therapy.

Cyclic-di-GMP stimulates keratinocyte innate immune responses and attenuates methicillin-resistant Staphylococcus aureus colonization in a murine skin wound infection model.

BACKGROUND: Staphylococcus aureus is a leading cause for morbidity and mortality associated with skin and burn wound infections. Therapeutic options for methicillin-resistant S. aureus (MRSA) have dwindled and therefore alternative treatments are urgently needed. In this study, the immuno-stimulating and anti-MRSA effects of cyclic di-guanosine monophosphate (c-di-GMP), a uniquely bacterial second messenger and immuno-modulator, were investigated in HaCaT human epidermal keratinocytes and a murine skin wound infection model. RESULTS: Stimulation of HaCaT cells with 125 µM c-di-GMP for 12 h prior to MRSA challenge resulted in a 20-fold reduction in bacterial colonization compared with untreated control cells, which was not the result of a direct c-di-GMP toxic effect, since bacterial viability was not affected by this dose in the absence of HaCaT cells. C-di-GMP-stimulated or MRSA-challenged HaCaT cells displayed enhanced secretion of the antimicrobial peptides human ß-defensin 1 (hBD-1), hBD-2, hBD-3 and LL-37, but for hBD1 and LL-37 the responses were additive in a c-di-GMP-dose-dependent manner. Secretion of the chemokines CXCL1 and CXCL8 was also elevated after stimulation of HaCaT cells with lower c-di-GMP doses and peaked at a dose of 5 µM. Finally, pre-treatment of mice with a 200 nmol dose of c-di-GMP 24 h before a challenge with MRSA in skin wound infection model resulted in a major reduction (up to 1,100-fold by day 2) in bacterial CFU counts recovered from challenged skin tissue sections compared PBS-treated control animals. Tissue sections displayed inflammatory cell infiltration and enhanced neutrophil influx in the c-di-GMP pre-treated animals, which might account for the reduced ability of MRSA to colonize c-di-GMP pre-treated mice. CONCLUSIONS: These results demonstrate that c-di-GMP is a potent immuno-modulator that can stimulate anti-MRSA immune responses in vivo and might therefore be a suitable alternative prophylactic or therapeutic agent for MRSA skin or burn wound infections.

Distribution and identification of Mycobacterium tuberculosis lineage in Kashgar prefecture.

OBJECTIVES: Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. METHODS: Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. RESULTS: M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). CONCLUSION: Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

The application of electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation for the treatment of vitiligo-associated leukotrichia.

Leukotrichia is one of the difficulties of vitiligo treatment. Hair follicle transplantation is an efficient method to treat vitiligo-associated leukotrichia. A trichiasis electrolyzer, commonly used for treating trichiasis, can be used to damage and remove the depigmented hair follicles. To evaluate the efficacy of the electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation for the treatment of vitiligo-associated leukotrichia. A total of 15 patients with stable vitiligo-associated eyebrow and eyelash leukotrichia were enrolled from Department of Dermatology, Hangzhou Third People's Hospital between January 2020 and January 2021. All patients were treated using a trichiasis electrolyzer combined with single hair follicle transplantation. The patients were followed up at the first week, the first month, the third month, and the sixth month after surgery. The texture and growth state of the transplanted hair were observed, and the number of surviving transplanted follicles and regenerating depigmented follicles were recorded. The transplanted hair grew as expected with natural shape. No local infection or obvious scar was observed. Most of the depigmented hair in the lesion area re-pigmented and only a few depigmented hairs regenerated. The average survival rate of the transplanted hair follicles was 71.6%, and the average regeneration rate of the depigmented hair was 11.6%. The electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation was an effective and safe method to treat vitiligo-associated leukotrichia.

ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2.

Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.

Altered circulating memory T cells in vitiligo cases followed NB-UVB therapy.

BACKGROUND: Vitiligo represents a commonly diagnosed autoimmune disease caused by the depletion of epidermal melanocytes. Many subsets of T cells contribute to vitiligo pathogenesis, including resident and circulating memory T cells. OBJECTIVES: To analyze the amounts of CD4+ and CD8+ memory T-cell subsets in peripheral blood specimens from vitiligo patients and alterations caused by narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Circulating CD4+ and CD8+ central memory T (TCM ) and effector memory T (TEM ) cell frequencies in 33 patients with non-segmental vitiligo and 16 healthy donors were evaluated by flow cytometry. Related chemokine levels were also detected. RESULTS: Peripheral blood CD4+ TCM and CD8+ TCM counts were markedly reduced in vitiligo cases while they were higher in active vitiligo compared with stable vitiligo cases. Circulating CD8+ TCM frequency in vitiligo was closely related to disease duration. Interestingly, CD4+ TCM and CD8+ TCM frequencies, alongside CXCL9 and CXCL10 amounts in peripheral blood of patients with vitiligo, were significantly decreased after NB-UVB phototherapy. CONCLUSIONS: Decreased frequencies of circulating CD4+ TCM and CD8+ TCM by NB-UVB suggest a possible immunosuppressive effect of phototherapy. The chemokines CXCL9 and CXCL10 are the bridge between circulating and skin resident memory T cells. NB-UVB blocks the homing of circulating memory T cells into vitiligo lesions by down-regulating CXCL9 and CXCL10. Targeting the above proteins could provide novel, durable treatment options to cure and prevent flares of this disease.

Tinea of vellus hair: shining under the Wood's lamp.

We herein reported a simple and cheap method to diagnose the tinea of vellus hair, which is long-neglected and always wrongly treated.

Repigmentation in two patients with vitiligo on AcEGCG 0.5% cream.

Per-acetylated epigallocatechin-3-gallate (AcEGCG), a fully acetylated derivative of EGCG, a more potent agent for protection of melanocytes from oxidative damage. We present two patients with vitiligo treated with AcEGCG 0.5% cream, who demonstrated skin repigmentation and control of depigmentation progression.

The Combination of the Mini-Punch Technique and Photodynamic Therapy for the Treatment of Mandibular Keloids and Hypertrophic Scars.

BACKGROUND: Mandibular keloids and hypertrophic scars can exert significant effects on the appearance of a patient. However, current treatments are not effective in all cases. Consequently, it is vital to identify a safe and effective treatment method. OBJECTIVE: To investigate the therapeutic effect of the mini-punch technique combined with photodynamic therapy (PDT) on mandibular keloids and hypertrophic scars. PATIENTS AND METHODS: Twenty patients with mandibular keloids and hypertrophic scars were enrolled, including 5 cases of keloids and 15 cases of hypertrophic scars, with a total of 40 lesions. The mini-punch technique was performed first, and then, PDT was conducted, once a week on 3 occasions in total. RESULTS: After 12 months of follow-up, 30 lesions had improved by more than 50%, thus achieving a good therapeutic effect. The Vancouver Scar Scale score of patients ranged between 8 and 12 points with a mean of 9.60 ± 1.09 points before surgery and between 2 and 9 points with a mean of 4.15 ± 2.05 points at 12 months after surgery. The mean Vancouver Scar Scale score after treatment was significantly lower than that before treatment (t = 11.80, p < .001). CONCLUSION: A combination of the mini-punch technique and PDT is an effective treatment for mandibular keloids and hypertrophic scars.