Effectiveness of digital psychological interventions in reducing perinatal depression: a systematic review of meta-analyses.

Digital psychological interventions have been widely used clinically in recent years, but the methodological quality and quality of evidence of related studies are unclear, thus interfering with the translation of practice outcomes and the application of clinical decisions. We searched for meta-analyses of randomized controlled trials in the PubMed, Web of Science, Embase, Cochrane Library, JBI Database, CINAHL, and PsycINFO databases as well as some databases containing gray literature up to 27 April 2022 using a combination of keywords. After two researchers independently screened and extracted data from the literature, the methodological quality of the included literature was evaluated by the AMSTAR 2 scale, and the evidence quality of the outcome index was graded by the Grading of Recommendations, Assessment, Development, and Evaluation system. A total of 12 meta-analyses reporting the positive impact of digital psychological interventions in the prevention and/or treatment of depressive symptoms in perinatal women were included, but the methodological quality and evidence level of the included studies were low. Digital psychological interventions are effective in reducing perinatal depression, but the methodological quality and reliability of outcome indicators are mostly low. Improving study designs, using higher-quality clinical evidence, conducting systematic evaluation studies strictly following the procedures, and standardizing the reporting of study results are recommended.

Anti-psoriasis activities of hydroxytyrosol on HaCaT cells under psoriatic inflammation in vitro.

BACKGROUND: Psoriasis is a prevalent chronic inflammatory dermatosis, which can significantly impact life quality of patients. The treatment of psoriasis is no cure and novel therapeutic options are urgently needed. Hydroxytyrosol (HT) possesses multiple biological activities, such as anti-inflammatory and anti-proliferation properties, suggesting its potential to counteract hallmarks of psoriasis. However, its role in the regulation of psoriasis remains unknown. OBJECTIVE: In the current study, we explored the anti-proliferative activity and anti-inflammatory responses of HT in psoriatic keratinocytes in vitro. METHODS: We used M5 cytokines cocktail, which includes tumor necrosis factor (TNF)-α, oncostatin-M, interleukin (IL)-17A, IL-1α, and IL-22, to simulate HaCaT cells to establish the cell model of psoriasis and explore the effects of HT on psoriasis in vitro. RESULTS: This study showed that HT exerted potent anti-inflammatory effect via influencing the expression of IL-6, IL-8, and TNF-α in M5-induced cell model of psoriasis. Moreover, it suppressed the expression of antimicrobial proteins in psoriatic keratinocytes. Additionally, it inhibited cell proliferation in psoriasis cell model. CONCLUSIONS: Altogether, our results suggested that HT has anti-psoriasis effects in vitro and HT may be a promising therapeutic agent in psoriasis treatment.

Intelligent Compound Fault Diagnosis of Roller Bearings Based on Deep Graph Convolutional Network.

The high correlation between rolling bearing composite faults and single fault samples is prone to misclassification. Therefore, this paper proposes a rolling bearing composite fault diagnosis method based on a deep graph convolutional network. First, the acquired raw vibration signals are pre-processed and divided into sub-samples. Secondly, a number of sub-samples in different health states are constructed as graph-structured data, divided into a training set and a test set. Finally, the training set is used as input to a deep graph convolutional neural network (DGCN) model, which is trained to determine the optimal structure and parameters of the network. A test set verifies the feasibility and effectiveness of the network. The experimental result shows that the DGCN can effectively identify compound faults in rolling bearings, which provides a new approach for the identification of compound faults in bearings.

Kynureninase contributes to the pathogenesis of psoriasis through pro-inflammatory effect.

Kynureninase (KYNU) is a key enzyme in the tryptophan metabolism pathway with elevated expression in psoriatic lesions relative to normal skin. However, whether KYNU contributes to the pathogenesis of psoriasis remains unknown. We sought to investigate the role of KYNU in psoriasis and its possible regulation mechanism. In the results, KYNU is upregulated in psoriatic skin samples from patients or animal models compared with normal skin control which was assayed in psoriatic patient samples, IMQ-induced psoriasis-like skin inflammation in BABL/c mice and M5-stimulated keratinocyte cell lines by immunohistochemistry (IHC). KYNU knockdown had a trivial impact on keratinocyte proliferation, but significantly inhibited the production of inflammatory cytokines in HaCaT, HEKα, and HEKn cells by quantitative reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot analysis. The 3'-untranslated region of KYNU contains a conserved target site of a skin-specific microRNA (miRNA), miR-203a, as predicted by TargetScan software. Furthermore, miR-203a exhibited an inversed expression kinetics to KYNU during the development of IMQ-induced psoriasis-like skin inflammation in BABL/c mice. Overexpression of miR-203 subsequently leading to the inhibition of KYNU, could significantly reduce the production of M5-induced, psoriasis-related inflammatory factors in keratinocytes. Finally, KYNU inhibitors could alleviate the pathological phenotypes in IMQ-mice. Our study supported the contributive role of KYNU in the development of psoriasis and provided preliminary evidence for KYNU as a potential therapeutic target in psoriasis.

Flexible and disposable gold nanoparticles-N-doped carbon-modified electrochemical sensor for simultaneous detection of dopamine and uric acid.

Catalytic and electrocatalytic applications of supported metal nanoparticles are hindered due to an aggregation of metal nanoparticles and catalytic leaching under harsh operations. Hence, stable and leaching free catalysts with high surface area are extremely desirable but also challenging. Here we report a gold nanoparticles-hosted mesoporous nitrogen doped carbon matrix, which is prepared using bovine serum albumin (BSA) through calcination. BSA plays three roles in this process as a reducing agent, capping agent and carbon precursor, hence the protocol exhibits economic and sustainable. Gold nanoparticles at N-doped BSA carbon (AuNPs@NBSAC)-modified three-electrode strip-based flexible sensor system has been developed, which displayed effective, sensitive and selective for simultaneous detection of uric acid (UA) and dopamine (DA). The AuNPs@NBSAC-modified sensor showed an excellent response toward DA with a linear response throughout the concentration range from 1 to 50 µM and a detection limit of 0.05 µM. It also exhibited an excellent response toward UA, with a wide detection range from 5 to 200 µM as well as a detection limit of 0.1 µM. The findings suggest that the AuNPs@NBSAC nanohybrid reveals promising applications and can be considered as potential electrode materials for development of electrochemical biosensors.

LncRNA RP6-65G23.1 accelerates proliferation and inhibits apoptosis via p-ERK1/2/p-AKT signaling pathway on keratinocytes.

Long non-coding RNAs (LncRNAs) play essential roles in the development of various diseases including hepatic carcinoma, melanoma, and psoriasis. Meanwhile, lncRNA-RP6-65G23.1 was upregulated in psoriasis. However, it is still unclear whether lncRNA-RP6-65G23.1 expression is upregulated and contributes to keratinocytes proliferation and apoptosis, and which mechanisms are responsible for these processes. The aims of this study are to address these issues. RP6-65G23.1 was significantly upregulated in M5-stimulated keratinocytes and stimulated the proliferation and inhibited the apoptosis of HaCaT cells. Knockdown of RP6-65G23.1 resulted in defects of growth and increased rates of apoptosis in HaCaT cells, while overexpression of RP6-65G23.1 manifested the opposite effects. Consistently, the expression of antiapoptotic proteins Bcl-xl and Bcl2 were decreased in RP6-65G23.1-knockdown cells but elevated in RP6-65G23.1 overexpression cells. In addition, RP6-65G23.1 depletion blunted the activity of extracellular regulated kinase 1/2 (ERK1/2) and AKT signaling pathways and induced G1 /S-growth arrest. By contrast, overexpression of RP6-65G23.1 activates the ERK1/2 and AKT signaling pathways and inhibits the expression of p21 and p27 in an AKT-dependent manner leading to promote the G1/S progression. Our results suggested that lncRNA-RP6-65G23.1 would contribute to the pathogenesis of psoriasis by regulating the proliferation and apoptosis of keratinocytes via the p-ERK1/2 and p-AKT pathways.

Suppression of malignant melanoma by knocking down growth differentiation factor-15 via inhibiting PTEN/PI3K/AKT signaling pathway.

Background: Melanoma is a highly malignant tumor, and it is characterized by high mortality. Growth differentiation factor 15 (GDF15) and PTEN/PI3K/AKT signaling pathway have been proved to be related with regulation of tumors. If GDF15 could regulate melanoma through targeting PTEN/PI3K/AKT signaling pathway remain unclear. Methods: EdU staining, wound healing, Transwell assay, and flow cytometry were performed to measure cell proliferation, migration, invasion, and apoptosis. GEPIA and TCGA data bases were applied to analyze the relationship between GDF15 and prognosis. Results: We found that high expression of GDF15 suggested lower survival of melanoma patients, and is positively linked with advanced stage through analysis with GEPIA and TCGA data bases. Knockdown of GDF15 greatly inhibited the migration, invasion and proliferation ability of both M14 and M21 cells, but promoted cell apoptosis. However, the influence of GDF15 on M14 and M21 cells were reversed by 740Y-P, the activator of PTEN/PI3K/AKT signaling pathway. In addition, 740Y-P significantly reversed the influence of sh-GDF15 on the epithelial-mesenchymal transition (EMT) related proteins expression in M14 and M21 cell lines. Significant higher expression of GDF15 in melanoma was observed. In addition, the inhibition of PTEN/PI3K/AKT signaling pathway by knocking down GDF15 was observed in both M14 and M21 cell lines. sh-GDF15 greatly decreased the resistance of M14 and M21 to chemotherapy drugs, docetaxel and doxorubicin. Conclusions: GDF15 regulated the cell proliferation, apoptosis, migration, invasion, and EMT process of M14 and M21 cell lines through targeting PTEN/PI3K/AKT signaling pathway. This research provides a novel prevention and treatment strategy for melanoma.

Carbon Fiber-Reinforced PLA Composite for Fused Deposition Modeling 3D Printing.

Polylactic acid (PLA) composite serve as widely used filaments in fused deposition modeling (FDM) 3D printing. This study investigates the enhancement of PLA composite's comprehensive mechanical properties and thermal stability through the incorporation of carbon fiber (CF). The influence of FDM process parameters on the mechanical properties of PLA composite is also analyzed. Results show that adding 5 wt.% CF significantly enhances the stiffness and comprehensive mechanical properties of PLA composite. The order of printing factors affecting the tensile strength of the PLA composite product is as follows: printing layer thickness, bottom plate temperature, printing speed, and nozzle temperature. Finally, optimal tensile strength is achieved under specific conditions: 0.1 mm layer thickness, 60 °C bottom plate temperature, 40 mm/s printing speed, and 215 °C nozzle temperature.

GPR15LG regulates psoriasis-like inflammation by down-regulating inflammatory factors on keratinocytes.

Psoriasis is a common chronic inflammatory skin disease characterized by aberrant proliferation of keratinocytes and infiltration of immune cells. We previously found that GPR15LG protein is highly expressed in psoriasis lesional skin and it positively regulates psoriatic keratinocyte proliferation. Our data also showed that GPR15LG could regulate the activity of NF-κB pathway, which is associated with psoriatic inflammation. In the present study, we demonstrated that Gpr15lg (ortholog of GPR15LG) knockdown attenuated the severity of imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Such an effect was achieved by down-regulating the expression of inflammatory cytokines interleukin (IL)-1α, IL-1ß, tumor necrosis factor (TNF)-α and S100A7. Consistently, GPR15LG knockdown in vitro significantly downgraded the expression of inflammatory factors in the cellular model of psoriasis. These results suggested that GPR15LG could be involved in the development of psoriasis by regulating inflammation.

Fabrication of flexible piezoelectric PZT/fabric composite.

Flexible piezoelectric PZT/fabric composite material is pliable and tough in nature which is in a lack of traditional PZT patches. It has great application prospect in improving the sensitivity of sensor/actuator made by piezoelectric materials especially when they are used for curved surfaces or complicated conditions. In this paper, glass fiber cloth was adopted as carrier to grow PZT piezoelectric crystal particles by hydrothermal method, and the optimum conditions were studied. The results showed that the soft glass fiber cloth was an ideal kind of carrier. A large number of cubic-shaped PZT nanocrystallines grew firmly in the carrier with a dense and uniform distribution. The best hydrothermal condition was found to be pH 13, reaction time 24 h, and reaction temperature 200°C.

Effects of Yishenjiangzhuo granules on immunity and bone metabolism in patients with stage 3-4 chronic kidney disease.

OBJECTIVE: To determine the effects of Yishenjiangzhuo granules (YJG) on bone metabolism and to explore the changes in levels of bone Gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), as well as their relationships with levels of B cells, regulatory T cells (Treg) and interleukin (IL)-17 in patients with stage 3-4 chronic kidney disease (CKD) before and after treatment. METHODS: Fifty-three stage 3-4 CKD patients were divided randomly into two groups: YJG treatment and control. Peripheral blood was taken from two groups of CKD patients and 21 healthy subjects in the normal group. The parameters determined were the levels of CD4+, CD19+, CD19+ CD69+, CD19+ av, Treg (CD4 + CD25 + CD127lo), BGP, TRAP, IL-17, calcium, phosphate, blood urea nitrogen, serum creatinine (SCr), hemoglobin (Hb) in peripheral blood, and urinary creatinine. Calcium-phosphate products and endogenous creatinine clearance rate (CCr) were calculated according to standard protocols. RESULTS: In YJG and control groups, SCr levels were lowered (P < 0.01) after treatment, whereas CCr (P < 0.05) as well as Hb and albumin levels (P < 0.01) were increased. The changes in levels of CCr and SCr in the YJG group were more significant. After treatment, CD19+CD69+ and Treg levels in the two groups varied (P < 0.01) compared with those of the normal group; the level of CD19+ increased but the levels of CD4+ and CD19 + AV decreased (P < 0.01) in both groups. Compared with the control group, the changes of CD19+ and CD19 + AV in the YJG group were more apparent (P < 0.05). Compared with the normal group, levels of IL-17 in both groups increased significantly (P < 0.01), and the difference in the control group was more significant (P < 0.05). After treatment, the TRAP level increased (P < 0.05), but the difference in BGP level (P > 0.05) was not significant. CONCLUSION: In stage 3-4 CKD patients, B cells and IL-17 participated in the induction of osteoclast activation. YJG could also elevate the level of B cells and decrease their apoptosis, but showed no significant effects on active B cells, IL-17 or osteoclast activity.

[Effect of modified sijunzi decoction on the bone metabolism of adriamycin induced nephropathy rats].

OBJECTIVE: To explore the effect of Modified Sijunzi Decoction (MSD) on the bone metabolism of prednisone intervened adriamycin-induced nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was prepared. Totally 50 SD rats were randomly divide into five groups, i.e., the model group, the hormone group, the Chinese medicine (CM) group, the CM + hormone group, and the normal control group. The 24-h urine samples were collected on the 7th, 21st, and 35th day after modeling. The 24-h urine protein was measured by biuret colorimetry. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), osteocalcin (BGP), and tartrate-resistant acid phosphatase (TRACP) were determined by ELISA. Expressions of OPG and RANKL in the tibia tissue were detected using real-time quantitative PCR and Western blot. RESULTS: (1) Compared with the normal control group, the 24-h urine protein increased in each group on the 7th, 21st, and 35th day (P < 0.05, P < 0.01). Compared with the model group, the 24-h urinary protein decreased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). The decrement was more obvious along with the treatment time went by (P < 0.05, P < 0.01). There was statistical difference in the reduction of urine protein on the 35th day between the CM group and the model group (P < 0.05). (2) Compared with the 21st-day of the same group, the serum levels of TRACP and RANKL increased (P < 0.05, P < 0.01). Compared with the model group, the serum levels of the TRACP and RANKL increased (P < 0.05, P < 0.01), OPG and BGP decreased (P < 0.05, P < 0.01) in the hormone group. Compared with the CM group at the same period, serum OPG level decreased and the RANKL level increased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). Besides, the serum level of TRACP increased and BGP decreased (P < 0.05, P < 0.01). Compared with the hormone group at the same period, OPG and BGP increased (P < 0.05, P < 0.01), RANKL decreased (P < 0.01) in the CM + hormone group. On the 35th day TRACP decreased (P < 0.01). (3) Compared with the normal group, mRNA expressions of OPG and RANKL on the 21st day increased (P < 0.05, P < 0.01), mRNA expressions of OPG and RANKL on the 35th day decreased in the model group (P < 0.01). Compared with the CM group at the same period, OPG mRNA expression decreased (P < 0.01) and RANKL mRNA expression increased in the hormone group (P < 0.05). OPG mRNA expression decreased in the CM +hormone group (P < 0.05). (4) Compared with the hormone group on the 21st day, the OPG level decreased and the RANKL protein increased (both P < 0.05). RANKL decreased in the CM + hormone group (P < 0.05). Compared with the model group at the same period, OPG decreased and RANKL increased in the hormone group (P < 0.01). Compared with the CM group at the same period, OPG decreased (P < 0.01), RANKL increased (P < 0.01) in the hormone group and the CM + hormone group. Compared with the hormone group at the same period, OPG increased and RANKL decreased in the CM + hormone group (both P < 0.01). CONCLUSIONS: Prednisone could induce osteoporosis through the OPG/RANKL/RANK pathway. MSZ could slow down the formation of prednisone-induced osteoporosis through promoting osteoblast differentiation, and inhibiting osteoclastogenesis.

Evaluating the effect of psychoeducational interventions on prenatal attachment and anxiety/depression in pregnant women and partners: A systematic review and meta-analysis.

BACKGROUND: Evidence about effective psychoeducational interventions to improve prenatal attachment, anxiety and depression has been increasing, but it lacks a complete synthesis of the results. The aim of this study is to evaluate the effect of psychoeducational intervention on prenatal attachment and anxiety/depression in pregnant women and their partners. METHODS: Ten databases were systematically searched to identify randomized controlled trials (RCTs) on the effectiveness of psychoeducational interventions on prenatal attachment from inception to March 2023, then manually screened to include studies of anxiety or depression. Two researchers assessed the methodological quality of the included studies using the Cochrane risk-of-bias tool and meta-analysis was performed using RevMan 5.4 software. RESULTS: Ten RCTs with a total of 700 pregnant women and 399 partners were included. Prenatal attachment scores after the intervention (standardized mean difference = 1.10, 95 % CI 0.65 to 1.55, P <.00001) was significantly increased and anxiety scores (standardized mean difference = -0.99, 95 % CI -1.18 to -0.80, P <.00001) was significantly lower. The subgroup analysis showed that the different prenatal attachment assessment tools were the source of heterogeneity in the combined results. The sensitivity analysis results showed reliable pooled results except for the studies using the self-made anxiety scale. CONCLUSION: This review suggests that psychoeducational interventions can effectively enhance prenatal attachment, reduce anxiety and depression, providing reference for the promotion of evidence-based practice of psychoeducational interventions in perinatal pregnant women and their partners.

Antitumor activity of synthetic three copper(II) complexes with terpyridine ligands.

Three new synthetic terpyridine copper(II) complexes were characterized. The copper(II) complexes induced apoptosis of three cancer cell lines and arrested T-24 cell cycle in G1 phase. The complexes were accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential. The complexes increased both intracellular ROS and Ca2+ levels and activated the caspase-3/9 expression. The apoptosis was further confirmed by Western Blotting analysis. Bcl-2 was down-regulated and Bax was upregulated after treatment with complexes 1-3. The in vivo studies showed that complexes 1-3 obviously inhibited the growth of tumor without significant toxicity to other organs.

In vitro and in vivo antitumor activities of Ru and Cu complexes with terpyridine derivatives as ligands.

Six terpyridine ligands(L1-L6) with chlorophenol or bromophenol moiety were obtained to prepare metal terpyridine derivatives complexes: [Ru(L1)(DMSO)Cl2] (1), [Ru(L2)(DMSO)Cl2] (2), [Ru(L3)(DMSO)Cl2] (3), [Cu(L4)Br2]·DMSO (4), Cu(L5)Br2 (5), and [Cu(L6)Br2]⋅CH3OH (6). The complexes were fully characterized. Ru complexes 1-3 showed low cytotoxicity against the tested cell lines. Cu complexes 4-6 exhibited higher cytotoxicity against several tested cancer cell lines compared to their ligands and cisplatin, and lower toxicity towards normal human cells. Copper(II) complexes 4-6 arrested T-24 cell cycle in G1 phase. The mechanism studies indicated that complexes 4-6 accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential, increase of the intracellular ROS levels and the release of Ca2+, and the activation of the Caspase cascade, finally inducing apoptosis. Animal studies showed that complex 6 obviously inhibited the tumor growth in a mouse xenograft model bearing T-24 tumor cells without significant toxicity.

Efficacy and Satisfaction Evaluation of Rapid Rehabilitation Nursing Intervention in Patients with Laparoscopic Myomectomy.

Objective: To evaluate the efficacy and satisfaction of rapid rehabilitation nursing in patients with laparoscopic myomectomy. Methods: In this retrospective study, a total of 60 patients scheduled for a laparoscopic myomectomy in our hospital from January 2019 to February 2022 were enrolled and assigned at a ratio of 1 : 1 to receive either routine nursing (routine group) or rapid rehabilitation nursing (study group) according to different nursing methods. Outcome measures included nursing efficiency and nursing satisfaction. Results: Rapid rehabilitation nursing resulted in less intraoperative blood loss, shorter postoperative exhaust time and hospital stay, and a lower incidence of bladder irritation (123.56 ± 30.68, 22.54 ± 5.07, 5.70 ± 1.06, and 4.55%) versus the routine nursing (185.78 ± 32.78, 31.02 ± 5.28, 7.57 ± 2.19, 18.18%) (P < 0.05). Rapid rehabilitation nursing was associated with a lower incidence of complications (3.33%) versus routine nursing (20.00%) (P < 0.05). The eligible patients receiving rapid rehabilitation nursing showed a significantly higher satisfaction (96.67%) versus routine nursing (80.00%) (P < 0.05). Conclusion: Rapid rehabilitation nursing is effective in the nursing of patients after laparoscopic myomectomy by minimizing the physical and mental stress of patients, shortening the length of hospital stay, reducing the occurrence of related complications, and boosting the quality of life of patients, so it is worthy of clinical application.

A rapid, one-step, variable-valence metal ion assisted reduction method for graphene oxide.

A process characterized by variable-valence metal (Mn, Co, Ni, etc) ion assisted reduction of graphene oxide with NaBH(4) heated at 90 °C for a short period of 1 h was developed to produce reduced graphene oxide (RGO), and the RGO sheets exhibited a homogeneous and stable dispersibility in water.

Array Integration and Far-Field Detection of Biocompatible Wireless LC Pressure Sensors.

In this paper, three configurations of LC (inductor-capacitor) pressure sensors are developed, namely series LC pressure sensors, compact LC pressure sensors, and far-field LC pressure sensor tags. The modified silk protein films have been chosen as substrates due to their good biocompatibility and air/water permeability, which is suitable for continuously pasting such substrates on skin. For series LC pressure sensors, conducting wire is used to connect the flexible capacitor and spiral inductor. It exhibits good cycling stability and high sensitivities, suitable for electronic skin. For compact LC pressure sensors, the spiral coil functions as inductor, antenna, and capacitor electrode simultaneously, minimizing the space cost and is suitable for array integration, while the sensitivities remain the same. By tailoring the turn of the spiral coil, the resonate frequency can be regulated continuously. An annular array of compact LC sensors with ten distinct resonate frequencies ranged from 400 to 1000 MHz is developed to remotely monitor the press of number 0-9. Finally, far-field LC pressure sensor tags with elongated detection distances are developed in which each compact LC sensor acts as a filter. A wireless in-shoe plantar to detect the sole pressure distribution using the far-field LC sensor configuration is developed.

Chinese herbal medicine bi min fang for allergic rhinitis: protocol for a double-blind, double-dummy, randomized controlled trial.

BACKGROUND: People with allergic rhinitis (AR) often seek help from Chinese medicine due to dissatisfaction with conventional treatments. Lung-spleen qi deficiency syndrome (LSQDS) is the most common type of AR, and the Chinese herbal medicine formula bi min fang (BMF) is commonly prescribed for AR patients with LSQDS. However, direct evidence supporting its efficacy and safety is not available, and its potential mechanism of action remains unclear. METHODS/DESIGN: This paper presents a double-blind, double-dummy, randomized controlled trial. After a 2-week run-in period, 80 AR patients with LSQDS will be recruited and randomly allocated to the BMF group or the control group in a 1:1 ratio. The patients in the BMF group will receive BMF and the placebo for levocetirizine hydrochloride orally, while the control group participants will receive levocetirizine hydrochloride and the placebo for BMF orally. All participants will receive 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is a change in the Total Nasal Symptom Score (TNSS). Secondary outcomes include changes in scores for the standard version of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), and visual analog scale (VAS); changes in serum levels of the cytokines interleukin-4, interferon-γ, transforming growth factor ß-1, and interleukin-17; and changes in the gut microbiota composition in the stool. The TNSS, RQLQ(S), and VAS will be recorded at the beginning of, middle of and after the treatment period and at the end of each month in the 3-month follow-up period. Blood and stool samples will be collected at baseline and the end of the treatment. The aforementioned four cytokines will be detected in the serum using enzyme-linked immunosorbent assays, and the stool gut microbiota will be detected using 16S ribosomal ribonucleic acid sequencing. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide consolidated evidence of the effect of BMF on AR and the potential mechanism by which BMF acts. This study will be the first to explore the mechanism of action of Chinese herbal medicine on the gut microbiota in AR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-17010970 . Registered on 23 March 2017.

Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via Phosphoinositide 3-Kinase/Akt Pathways.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. CRNN is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of five pro-inflammatory cytokines (i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α). Lentiviral expression of CRNN increased cell proliferation by inducing cyclin D1. Conversely, knockdown of CRNN by small interfering RNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase and Akt. Inactivation of the phosphoinositide 3-kinase and Akt pathways using small interfering RNA or selective inhibitors (LY294002 and MK2206) reduced the proliferative effects of CRNN. Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.