Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Objective:To investigate difficult-to-treat sites in patients with psoriasis receiving biological therapy.Methods:Clinical data were retrospectively collected from 73 adult patients with psoriasis in the database of Psoriasis Center, National Clinical Research Center for Skin and Immune Diseases from June 2020 to September 2021, who had received sufficient and standardized treatment with biological agents for ≥ 24 weeks, and were still treated with biological agents at the time of enrolment into this study with the psoriasis area and severity index (PASI) score being 1 - 5 at the time of enrolment into the database of Psoriasis Center. Distribution of psoriatic lesions resistant to biological therapy were analyzed, and differences in refractory sites were compared between different biologics. Chi-square test or Fisher′s exact test was used to analyze differences in the anatomical distribution of residual skin lesions after treatment with different biologics, McNemar test to compare the anatomical distribution of skin lesions before and after biological therapy, and Kruskal-Wallis H test to analyze the association between PASI scores for residual skin lesions and dermatology life quality index (DLQI) scores. Results:After ≥ 24 weeks of sufficient and standardized biological therapy in the 73 patients, refractory skin lesions mostly involved the lower limbs (46 cases, 63.01%) , followed by the scalp (36 cases, 49.32%) and upper limbs (27 cases, 36.99%) ; proportions of patients with residual skin lesions on the face and neck, trunk, upper limbs, lower limbs, hands and feet significantly decreased after biological therapy compared with those before treatment (paired χ2 = 5.14, 7.69, 9.90, 4.17 and 6.13, P = 0.016, 0.003, 0.001, 0.031 and 0.008, respectively) , while there was no significant difference in the proportions of patients with skin lesions on the scalp and genital areas before and after treatment (both P > 0.05) . No significant difference in the anatomical distribution of residual skin lesions was observed between the 13 patients receiving treatment with tumor necrosis factor inhibitors (adalimumab, infliximab, or tumor necrosis factor receptor-antibody fusion protein) and 59 receiving treatment with interleukin-17 (IL-17) inhibitors (secukinumab or ixekizumab) (all P > 0.05) . There was no significant difference in the anatomical distribution of residual skin lesions in the 13 patients before and after the treatment with tumor necrosis factor inhibitors (all P > 0.05) ; in the 59 patients treated with IL-17 inhibitors, the proportions of patients with residual skin lesions on the trunk, upper limbs, hands and feet significantly decreased after treatment (paired χ2 = 4.90, 9.09 and 7.11, P = 0.021, 0.001 and 0.004, respectively) , while there was no significant difference in the distribution of skin lesions on the scalp, face and neck, lower limbs and genital area before and after treatment (all P > 0.05) . Among the 73 patients, the PASI scores for lesions on the upper and lower limbs and the total PASI scores were all associated with the DLQI scores ( H = 7.52, 12.61, 6.75, respectively, all P < 0.05) , and were significantly higher in the patients with DLQI scores of > 10 points than in those with DLQI scores of ≤ 5 points (all P < 0.05) . Conclusions:Biological therapy-resistant psoriatic lesions were mostly located on the scalp, and refractory skin lesions mostly involved the lower limbs, scalp and upper limbs. No significant difference in the anatomical distribution of residual skin lesions was observed between patients treated with tumor necrosis factor inhibitors and IL-17 inhibitors, but IL-17 inhibitors may result in lesion clearance at more anatomical sites compared with tumor necrosis factor inhibitors.

Objective: To observe the effect of chorioamnionitis on placental microvessel and platelet metabolism in premature and the correlation between them. Methods: With clinical randomized controlled trial (RCT), the cases were matched by 11 according to gestational ages and divided into 2 groups according to the placental pathology results: chorioamnionitis group and control group, 32 cases in each group.Dates were obtained for preterm infants (gestational age<37 weeks) admitted to the Department of Neonatology at Guangdong Women and Children Hospital, born between June and December 2016.The platelet parameter [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT)], birth weight, thrombocytopenia, hemorrhage complication, miscrovascular density (MVD) in placenta, platelet activating factors (CD_62p, CD₆₃) and thrombopoietin (TPO) in preterm infants were recorded and compared. Results: In chorioamnionitis group, the infant birth weight[(1.90±0.41) kg vs.(2.31±0.62) kg] and the PLT in 72 hours [<24 h (197.97±63.43)×10⁹/L vs.(266.34±69.92)×10⁹/L; 24-72 h (202.28±29.70)×10⁹/L vs.(256.38±69.96)×10⁹/L] were significantly lower compared with the control group, and the differences were statistically significant(all P<0.05). The incidence of early thrombocytopenia(37.50% vs.9.38%), intracranial hemorrhage(40.62% vs.15.63%), MPV [(8.73±0.89) fL vs.(8.27±0.64) fL] and PDW[(59.46±5.90)% vs.(55.20±5.37)%] in 24 hours were significantly higher in chorioamnionitis group, and the differences were statistically significant (all P<0.05). The placental MVD in chorioamnionitis group significantly decreased[(9.08±1.35)% vs.(12.89±1.36)%, P<0.05 ]. The level of CD_62p, CD₆₃ and TPO in umbilical cord blood were significantly higher in chorioamnionitis group[(25.37±5.20)% vs.(10.35±2.94)%, (9.49±1.58)% vs.(4.04±1.21)%, (271.08±197.22) μg/L vs.(141.87±78.10) μg/L, all P<0.05]. The placental MVD was positively associated with PLT (r=0.74, P<0.05) and negatively associated with CD_62p, CD₆₃ and TPO among infants with chorioamnionitis (r=-0.64, -0.44, -0.44, all P<0.05). Conclusions The chorioamnionitis may decrease the MVD in placenta and activate platelet in fetal circulation, damaged placental microvessel may activate platelet further.