3-phosphoinositide dependent kinase-1 (PDK1) has been shown to be a critical regulator of the PI3K-Akt pathway.PDK1 can activate Akt and participates in the activation of PI3K-Akt signaling pathway to promote tumor development,invasion and metastasis.At present,it has been found that PDK1 is highly expressed in head and neck cancer,multiple myeloma,pancreatic cancer,esophageal cancer,colon cancer and other malignant tumors.Thereby inhibiting PDK1 overexpression may provide a new breakthrough for the treatment of malignant tumor.At present,many kinds of PDK1 inhibitors have been put into production,which plays an important role in tumor therapy.

Objective:To investigate reflectance confocal microscopic features of childhood scabies, and to analyze clinical significance of reflectance confocal microscopy (RCM) in the diagnosis and treatment of childhood scabies.Methods:A retrospective analysis was performed in 77 children with confirmed scabies at Department of Dermatology, Tianjin Children′s Hospital from April 2018 to October 2019. These patients were divided into negative treatment history group (61 cases) and positive treatment history group (16 cases) . All the patients underwent RCM and microscopic examination of skin scrapings.Results:Among the 77 children with scabies, positive microscopic examination results were found in 33 (42.86%) , including 28 in the negative treatment history group and 5 in the positive treatment history group. Burrows, sarcoptid mites or their eggs and fecal pellets were observed in 56 cases (72.73%) by RCM, including 49 (80.33%) in the negative treatment history group and 7 in the positive treatment history group. RCM showed a significantly increased overall positive rate compared with microscopy of skin scrapings ( χ2=14.08, P<0.05) . In the negative treatment history group, RCM also showed a significantly increased positive rate compared with microscopy of skin scrapings ( χ2=15.53, P < 0.05) . Conclusion:RCM is of high clinical value to the diagnosis and treatment of childhood scabies.

Objective To compare the infectivity of several transformed Chlamydia trachomatis (Ct) mouse pneumonitis (Mopn) strains to host cells, and to identify cell invasion-related virulence genes in Chlamydial plasmids. Methods Several Ct strains, including wild-type Ct Mopn strain(WT strain), plasmid-free Ct strain(CMUT3 strain), Ct Mopn strain transformed with the shuttle vector carrying pGFP and the complete C. muridarum (CM) plasmid (pGFP::CM strain)and Ct Mopn strains transformed with shuttle vectors carrying pGFP and mutant CM plasmids with in-frame deletions of Pgp3, 4, 5 or 7 (pGFP::CM△Pgp3, 4, 5, 7 strains), were cultured, amplified and collected. After the concentrations of Ct were determined, each of these strains was divided into four groups to be inoculated at a same amount(1.5 × 104 inclusion forming units(IFU)) followed by four different treatments respectively: centrifugalization +DEAE group treated with centrifugalization followed by ion-exchange chromatography on diethylaminoethyl(DEAE)-cellulose columns, centrifugalization group treated with centrifugalization only, DEAE group treated with chromatography on DEAE-cellulose columns only, control group receiving no treatment. After additional culture for 20 - 24 hours, indirect immunofluorescence assay was performed to count the number of chlamydial inclusions. At 20, 40 and 60 hours after infection, the growth rate and area of chlamydial plaques were assessed after three continuous passages. Lugol′s iodine staining was conducted to observe glycogen synthesis in bacterial inclusions. Results The inclusion number in the centrifugalization + DEAE group, centrifugalization group, DEAE group and control group was 10.20 ± 1.30, 6.80 ± 0.44, 3.00 ± 1.22 and 0.80 ± 0.45 respectively for the pGFP::CM△Pgp4 strain, 6.40 ± 0.89, 3.80 ± 0.83, 1.60 ± 0.89 and 0.60 ± 0.54 respectively for the CMUT3 strain. Under same experiment conditions, the pGFP::CM△Pgp4 strain and CMUT3 strain showed similar infectivity, and formed less inclusions compared with the other Ct strains (all P < 0.01). The number of inclusions formed by the same Ct strains were significantly different among the 4 groups(F = 845.310, P <0.01), and were highest in the centrifugalization + DEAE group for all the strains. The pGFP::CM△Pgp4 strain showed significantly lower growth rate and area of plaques with an abnormality in glycogen accumulation compared with the other strains at 20, 40 and 60 hours after infection. Conclusion The plasmid-encoding gene Pgp4 may be a cell invasion-associated virulence gene in chlamydial plasmids.

Objective To evaluate the clinical application value of reflectance confocal microscopy(RCM) in the diagnosis of several common diseases manifesting as papules in children, including lichen nitidus, verruca planae, lichen striatus, milium, molluscum contagiosum and lichen pilaris. Methods A total of 579 children clinically characterized by papules were recruited into this study. RCM was used to observe lesions and perilesional normal skin. The RCM features of 6 diseases manifesting as papules were analyzed and compared. Results Based on RCM images, 236 patients were diagnosed with lichen nitidus, 70 with verruca planae, 123 with lichen striatus, 40 with milium, 53 with molluscum contagiosum and 57 with lichen pilaris. All the 6 diseases had typical RCM features. Concretely speaking, RCM images of lichen nitidus lesions showed infiltration of dense inflammatory cells and melanophages in enlarged dermal papillae. In RCM images of verruca planae lesions, cells in the granular and spinous layers were arranged in concentric circles, giving a rose cluster?like appearance. RCM images of lichen striatus lesions revealed focal swelling of stratum spinosum, absent or local liquifaction degeneration of basal cells, and clustering of a moderate number of inflammatory cells in the superficial dermis. In RCM images of milium lesions, well?circumscribed round or oval structures containing highly but nonuniformly refractive materials could be seen in the dermis. RCM images of molluscum contagiosum lesions showed intact cystoid structures containing highly refractive molluscum bodies. Lowly to moderately refractive cutin ? like materials were observed along with the dilation of hair follicle infundibula in RCM images of lichen pilaris lesions. In RCM images, the 6 diseases were distinguished mainly based on structural features(patterns and refractivity)of skin lesions shown by continuous vertical scanning. Conclusion RCM is of great value to the diagnosis of diseases manifesting as papules in children.

Objective To analyze the components of attentional bias on anger and disgust emotional faces in college students with social anxiety disorder.Methods DSM-V was used for clinical diagnosis after the initial screening with Interaction Anxiousness Scale.The subjects meet the inclusion criteria were divided into social anxiety disorder group (SAD group) and healthy control group (HC group).Koster's improved dot-probe paradigm was used in a 2 (group:SAD group,HC group) ×2 (emotion categories:anger,disgust)mixed-design experiment,and the different characteristics of attentional bias between the two groups on different emotional faces were compared.Results In SAD group,under the condition of angry faces,the response times to the probe targets with the same or different positions from the negative faces were (369.7±53.0)ms and (447.2±54.3) ms,while the response times were (429.6±70.2) ms and (444.2±55.8) ms under the condition of disgust faces,and the SAD group showed attentional bias towards both anger and disgust faces (t =24.15 and 2.45,P＜0.05).Under the condition of anger faces,the response time of HC group to the consistent and inconsistent position of probe target were (466.9±40.0) ms and (483.8±43.8) ms,and the HC group had an attentional bias towards anger faces(t=6.58,P＜0.05).The response time under disgust faces was (493.8±43.6)ms and (498.0±46.7)ms in HC group,and did not show an attentional bias towards disgust(t=1.65,P=0.108).The scores of attentional orientation to anger faces in SAD group were significantly higher than those in the HC group(F=19.26,P＜0.001),but there was no significant difference between the two groups towards disgust faces (F=0.02,P=0.897).Compared with disgust faces,the attentional orientation to anger faces was faster in both HC and SAD groups (F=101.66 and 8.00,P＜0.05).Compared with the HC group,the SAD group had an impaired attentional disengagement from anger faces(F=8.66,P=0.004).Conclusion The students with social anxiety disorder have attentional bias towards both anger and disgust facial expressions,which manifested as facilitated attentional orientation and impaired attentional disengagement to anger faces.

Objective:To evaluate the clinical efficacy and safety of adalimumab combined with acitretin in the treatment of childhood generalized pustular psoriasis.Methods:Five children with generalized pustular psoriasis were collected from Department of Dermatology, Tianjin Children′s Hospital from October 2019 to August 2020. After admission, the patients received oral acitretin at a dose of 0.5 mg·kg -1·d -1. After relevant laboratory examinations, these patients additionally received subcutaneous injections of 20- or 40-mg adalimumab at weeks 0 (the initial dose) , 1, and every 2 weeks thereafter; when patients obtained a 50% improvement in the Japanese Dermatology Association (JDA) severity index score, the dose of acitretin would be reduced to 0.3 mg·kg -1·d -1, and acitretin would be discontinued after a 75% improvement. The disease condition was evaluated at weeks 0, 1, 2, 4, 8, 12 and 24 after the start of adalimumab treatment, and adverse reactions were monitored during treatment. Results:All the 5 patients received drug treatment for at least 40 weeks. After 2-week treatment, 3 patients achieved a 50% reduction in JDA severity index score (JDA50) ; after 4-week treatment, 4 achieved JDA75, and 1 achieved JDA100; after 8-week treatment, all the 5 patients achieved JDA100. By June 2021, all the 5 children received follow-up for at least 40 weeks, no recurrence was observed during the treatment period, and no infections, malignant tumors or other serious adverse reactions occurred.Conclusion:Adalimumab combined with acitretin shows rapid onset of action and high safety in the treatment of childhood generalized pustular psoriasis.

Objective:To explore the role of systematic wound management in the treatment of Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) in children.Methods:Clinical data were collected from 5 children with SJS/TEN, who were admitted to the Department of Dermatology, Tianjin Children′s Hospital from October 2019 to August 2021, and retrospectively analyzed to investigate the role of systematic management of the skin and mucosa wound besides drug therapy in the treatment of SJS/TEN.Results:The 5 patients, including 1 case of SJS, 1 case of SJS/TEN overlap syndrome, and 3 cases of TEN, were aged 2 to 13 years, and were cured and discharged after the treatment with intravenous methylprednisolone and systematic wound management. Among the 5 children, the severity of TEN scores (STENS) were 18.6 ± 1.9 points at admission, and 13.8 ± 1.9, 4.4 ± 0.5, and 2.0 ± 0.7 points on days 7, 10, and 14 during hospitalization, respectively; the time to complete re-epithelialization was 10.0 ± 2.1 days, and the length of hospital stay was 14.4 ± 4.2 days. During 4-month multidisciplinary follow-up, no scars or complications of the eyes, mouth, genitalia, or lungs occurred.Conclusion:Systematic wound management is helpful to control the progress of SJS/TEN, accelerate wound healing, and improve patients′ quality of life.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*