Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective:To explore the influence of temperament between parenting style and externalizing problem behaviors in school-age children.Methods:In October 2017, a stratified cluster sampling method was used to conduct a questionnaire survey among 380 school-age children in Aruhorqin Banner, Chifeng City, Inner Mongolia Autonomous Region. All the school-age children were assessed by the Achenbach child behavior checklist, parenting style scale, and middle childhood temperament questionnaire.Mediation models were established by the PROCESS macro program of SPSS, and the mediating effect was tested by the Bootstrap method.Results:The scores of various scales for school-age children were as follows: father's authoritative parenting style(3.77±1.11), father's authoritarian parenting style(1.55±0.68), father's indulgent parenting style(1.25±0.57), mother's authoritative parenting style(3.86±1.16), mother's authoritarian parenting style(1.64±0.73), mother's indulgent parenting style(1.25±0.61), activity level(2.42±0.71), attention dispersion(3.78±0.81), externalization problem behaviors 3.0(4.0).For school-age children, the scores of externalization problem behaviors were negatively correlated with the scores of authoritative parenting style( r=-0.15, -0.11, both P<0.05), and positively correlated with authoritarian and indulgent parenting style ( r=0.17-0.33, all P<0.05). The scores of externalization problem behaviors were positively correlated with eight temperament dimensions, such as adaptability, emotional essence, reaction threshold, attention dispersion, persistence, rhythmicity, activity level and reaction intensity( r=0.17-0.42, all P<0.05). After controlling for age and gender, attention dispersion played a masking effect on the influence of authoritative parenting style on children's externalizing problem behaviors, with the indirect effect accounting for 21.05%(|0.04/-0.19|) and 26.67%(|0.04/-0.15|) of the direct effect respectively. Attention dispersion partially mediated the impact of father's authoritarian parenting style on children's externalization problem behaviors, with the mediating effect accounting for 10.71%(0.03/0.28) of the total effect. Response intensity partially mediated the impact of authoritarian parenting style on children's externalizing problem behaviors, with the mediating effect accounting for 25.00%(0.07/0.28) and 27.58%(0.08/0.29) of the total effect respectively. Conclusion:Temperament plays a mediating role between parenting styles and externalizing problem behaviors among school-age children. A nurturing environment suitable for children's temperament should be created to prevent the occurrence of externalizing problem behaviors among school-age children.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

BACKGROUND:Numerous clinical studies have suggested a close relationship between obesity and osteoporosis,but whether there is a genetic causal effect between obesity and osteoporosis remains unclear. OBJECTIVE:To explore the association between obesity and osteoporosis using summary data from a large-scale genome-wide association study(GWAS)through Mendelian randomization analysis. METHODS:Obesity data were derived from summary statistics of the Genetic Investigation of Anthropometric Traits(GIANT)and the UK Biobank(UKBB).Osteoporosis data were obtained from the Genetic Factors for Osteoporosis(GeFOS)consortium,including two bone density phenotypes:total body bone mineral density(BMD)and heel BMD.The inverse variance-weighted method was the primary analysis,with the Mendelian randomization method based on Egger regression(MR-Egger)and weighted median method as supplementary approaches to calculate the causal association between genetic variations related to obesity and osteoporosis.Sensitivity analyses were conducted to validate the reliability of the results.Heterogeneity was assessed using Cochran's Q test.Horizontal pleiotropy was assessed through the MR-Egger intercept test.Leave-one-out analysis was performed to evaluate the potential influence of single nucleotide polymorphisms on the combined inverse variance-weighted estimates. RESULTS AND CONCLUSION:(1)Impact of obesity on osteoporosis:In addition to body mass index and forearm BMD,body mass index,waist-to-hip ratio,body mass index-adjusted waist-to-hip ratio,and whole-body body mass index,heel BMD,forearm BMD,lumbar spine BMD,and femoral neck BMD were causally related to each other.Further Meta-analysis revealed that obesity increased the risk of BMD(odds ratio=1.07,95%confidence interval:1.03-1.12,P<0.01).(2)Impact of osteoporosis on obesity:Apart from arm BMD and lumbar spine BMD as exposure factors showing causal relationships with obesity,other datasets indicated no causal effect between total body BMD,heel BMD,femoral neck BMD,and obesity.Additional meta-analysis demonstrated that BMD did not increase the risk of obesity(odds rate=0.99,95%confidence interval:0.98-1.01,P<0.01).There is a causal relationship between obesity and osteoporosis,suggesting that obesity may be a risk factor for osteoporosis.However,no causal association is found between osteoporosis and obesity.

Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

Objective To compare the sensitivity and accuracy of amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA) and magnetic particles-based chemiluminescence immunoassay (MP-CLIA) for detection of staphylococcal enterotoxin C (SEC) in the simulated milk samples. Methods The AlphaLISA was constructed using goat anti-SEC polyclonal antibody-coupled receptor microspheres, biotin-labeled SEC monoclonal antibody and streptavidin-coupled donor microspheres. The MP-CLIA was constructed using goat anti-SEC polyclonal antibody conjugated alkaline phosphatase, biotin-labeled anti-SEC monoclonal antibody and streptavidin conjugated magnetic beads. Results The sensitivity of AlphaLISA to detect SEC content in simulated milk samples was 4.04 ng/L, and the coefficient of variation (CV) was 1.98%~9.82%. The sensitivity of MP-CLIA was 108.19 ng/L and CV was 4.63%~20.40%. Conclusion Compared with MP-CLIA, AlphaLISA is more sensitive and accurate to detecting SEC.
Animals ; Streptavidin ; Biotin ; Luminescence ; Milk ; Antibodies, Monoclonal ; Goats ; Immunoassay/methods*

Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.

Objective: To investigate the outbreak of mumps in a remote village school of Zhaoqing City, to evaluate and vaccine effectiveness ( VE ) of mumps containing vaccine (MuCV), so as to provide reference for the formulation of epidemic prevention and control strategies. Methods: Through on site case investigations and interviews, case data and epidemic related epidemiological information were obtained. Descriptive and retrospective cohort studies were used to analyze the epidemic characteristics, explore risk factors, and evaluate the protective effect of vaccines. Results: Totally 166 cases of mumps were found, and all of them were students. The total attack rate was 7.79% and the outbreak lasted for 60 days. The first case occurred on October 11th and the last case occurred on December 9th in 2018. Most of the cases aged from 10 to 13 years old, accounting for 66.27%. There were 96 male patients and 70 female patients, with no statistically significant sex difference in the incidence rate ( χ 2=2.40, P >0.05). Involving 28 classes, 11 of which had an incidence rate more than 10%, mainly distributed in grades 2, 4 and 6. There were statistically significant differences in incidence rates among different grades ( χ 2=96.89, P <0.01) and different floors ( χ 2=67.35, P < 0.01 ), with the third floor higher than the other floors. Twelve out of 58 boarding pupils were cases, and boarding pupils were 1.89 times higher in risk of contracting mumps than day students ( RR=1.89, 95%CI =1.10-3.23). Pupils without being given the shot of MuCV were higher in the infection rate than those having the shot ( χ 2=5.70, P <0.05), and the VE % was 35% (95% CI = 7%- 55%). The VE % of one dose was 34% (4%-54%), while the effectiveness of protection was declined with time ( χ 2 trend =6.53, P < 0.05). The effectiveness of vaccine almost diasappeared six years after the shot ( χ 2=1.12, P >0.05). Conclusion Delayed case report and isolation, low rate of receiving MuCV, and decreasing effectiveness of one shot MuCV are closely assocaited with the outbreak and ongoing spread of the epidemic.

This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.