ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8⁺ T cells were transformed into CD4⁺ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To investigate the impact of daily step count on glycemic outcomes in community residents with impaired glucose tolerance (IGT).Methods:This was a prospective cohort study, in October 2018, 204 residents who met the criteria of IGT were recruited in the Shijingshan District in Beijing. The subjects were tested for fasting blood glucose, oral glucose tolerance test 2-hour blood glucose (2hBG), glycated hemoglobin A 1c (HbA 1c), lipid profile, liver and kidney function, as well as measurements of height, weight and waist circumference. A dedicated mobile application was used to deliver prediabetes health knowledge monthly. Online guidance was provided to answer questions and daily step count was collected using the application. Three years later, a follow-up was conducted to assess the participants′ glycemic outcomes and other indexes, and a total of 142 participants completed the follow-up review. According to daily step count, the subjects were categorized into high step count group (42 cases,>7 000 steps daily), moderate step count group (54 cases, 5 000-7 000 steps daily), and low step count group (46 cases,<5 000 steps daily). Subjects were categorized into diabetes group (30 cases), prediabetes group (77 cases) and normal glucose tolerance group (35 cases) with glycemic outcomes. Independent sample t test was used to compare the differences in blood glucose, blood lipids, and step counts between the two groups. Kruskal-Wallis H test or one-way ANOVA was used to compare the differences in blood glucose, blood lipids, and step counts between multiple groups. The χ2 test was used to compare the differences in glycemic outcomes between multiple groups. Multivariate logistic regression analysis was used to assess the impact of daily step counts and body mass index on glycemic outcomes. Linear regression analysis was used to evaluate the relationship between daily step counts and 2 h BG. Results:A total of 142 participants completed the 3-year follow-up, including 43 males and 99 females, with a mean age of (60.15±5.67) years. At baseline, males had significantly higher body mass index, waist circumference, and fasting blood glucose when compared to those in females [(26.97±2.43) vs (24.89±2.93) kg/m 2, (92.68±7.75) vs (83.83±8.60) cm, (5.83±0.61) vs (5.62±0.52) mmol/L], the total cholesterol and HDL-C were also significantly lower in males than those in females [(5.10±1.16) vs (5.55±0.95) mmol/L, (1.35±0.34) vs (1.56±0.35) mmol/L] (all P<0.05). After 3-year follow-up, 21.1% (30/142) of IGT participants progressed to diabetes, with an annual conversion rate of approximately 7%. The normal glucose tolerance group showed significantly higher daily step counts when compared with the prediabetes and diabetes groups [(7 886±2 867) vs (5 981±2 655) vs (4 117±2 674) steps] ( H=31.778, P<0.001). Individuals with higher daily step counts exhibited lower body mass index, 2 h BG, and HbA 1c level when compared with those in the ones with moderate and low step counts [(24.26±3.09) vs (25.44±3.38) vs (26.26±3.59) kg/m 2, (7.50±1.71) vs (9.15±3.30) vs (11.19±3.84) mmol/L, 5.97%±0.46% vs 6.14%±0.99% vs 6.40%±0.96%] (all P<0.05). Higher step count was positively correlated with the reversal of prediabetes to normal blood glucose levels (moderate step count, OR=0.297, 95% CI: 0.109-0.804; low step count, OR=0.055, 95% CI: 0.010-0.287), lower daily step count correlated positively with prediabetes progressing to diabetes ( OR=4.857, 95% CI: 1.140-20.689) (all P<0.05). For every additional 1 000 steps per day, the 2 h BG decreased by 0.5 mmol/L. Conclusion:As daily step count increases, the glucose metabolism improves in IGT community residents. Higher daily step count is associated with reversal of IGT to normal glucose tolerance, while lower daily step count may be associated with the progression of IGT to diabetes.

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*