ObjectiveTo detect the mRNA expression levels of RORγt and Foxp3 genes in peripheral blood mononuclear cells(PBMCs) of children with atopic dermatitis(AD),and to explore their possible roles in the development of AD.MethodsSixty-three children with AD and 54 age-matched normal children were eligible for this study.Real-time fluorescence-based quantitative PCR was carried out to measure the mRNA expressions of RORγt and Foxp3 genes in PBMCs of these subjects.ResultsThe relative expression levels of Foxp3 and RORγt mRNA were significantly higher in children with AD compared with the normal controls (2.4060 ± 0.3355 vs.1.1852 ± 0.4189,t =17.50,P＜ 0.01; 6.9130 ± 0.2046 vs.2.7501 ± 0.2518,t =98.63,P ＜ 0.01 ).A statistical increase was observed in the level of RORγt mRNA in children with severe AD compared with children with mild and moderate AD(7.1203 ± 0.1056 vs.6.8046 ± 0.1731 and 6.8655 ± 0.3671,t =6.61,5.23,both P ＜ 0.01).No significant difference was noted in the expression of RORγt mRNA between children with mild and moderate AD,or in the Foxp3 mRNA expression among children with mild,moderate and severe AD.The severity of AD was positively correlated with the level of RORγt mRNA (r =0.62,P ＜ 0.01 ),but uncorrelated with the level of Foxp3 mRNA(r =0.04,P ＞ 0.05).ConclusionsThe high expressions of RORγt and Foxp3 genes may be involved in the pathogenesis of AD,and the severity of AD is positively correlated with the expression intensity of RORγt gene.

Objective To explore the role of Toll like receptor 2 (TLR2) in the pathogenesis of acne vulgaris. Methods Venous blood was collected from 30 normal human controls and 90 patients with acne vulgaris. The patients were equally divided into three groups, i.e., mild, moderate and severe groups, according to disease severity. Flow cytometry was performed to detect the expression of TLR2 in PBMCs, and double antibody sandwich ELISA to measure the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). Results A significant increase was observed in the expression of TLR2 in PBMCs, serum level of IL-8and TNF-α in the three groups of patients with acne vulgaris compared with the normal human controls (all P ＜0.01). The expression of TLR2 was positively correlated with the expression of IL-8 (r=0.382, 0.517,0.436,respectively, all P＜0.05) and TNF-α(r=0.641, 0.725, 0.593, respectively, all P＜0.05) in the patients with mild, moderate and severe acne vulgaris, respectively, and with the severity of acne vulgaris (r = 0.406,P＜0.01 ). Conclusion The expression level of TLR2 and related cytokines seems closely correlated with the severity of acne vulgaris.

Background and purpose: When patients have positive sentinel lymph node (SLN), axillary lymph node dissection (ALND) is usually performed, but most of them have no metastasis in the non-sentinel lymph node (nSLN). It is of great significance to predict metastasis of nSLN precisely. The aim of the study was to establish a nomogram for the intraoperative prediction of nSLN metastasis in breast cancer patients using one-step nucleic acid amplification (OSNA) techniques and to direct the subsequent therapy for breast cancer effectively. Methods: Of 552 breast cancer patients who underwent SLN biopsy in the 2010 OSNA clinical trial, 103 with SLN metastasis treated with ALND were assessed to establish a nomogram for intraoperative prediction of nSLN based on the molecular diagnosis. A validation cohort of 61 patients who met the similar criteria in the 2015 OSNA clinical trial subsequently validated it. Results: Primary tumor size, total tumor load, the number of positive SLNs and negative SLNs were associated with the presence of nSLN metastasis based on the multivariable logistic regression results, and a nomogram was established with these variables. Its area under the ROC curve was 0.814 for the predictive model and it was 0.842 in the re-validation cohort. The tumor size assessed by the postoperative histological examination was replaced by the size evaluated by the imaging examination, and the area under the ROC curve was 0.838. There was no statistically significant difference in the accuracy compared with the former validation data (P=0.7406). Conclusion: The predictive nomogram based on the molecular diagnosis can predict the nSLN metastases intra/post-operatively. It appears to be obviously superior to other predictive models and may help to guide the axillary management and to make decisions about radiation target region.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.

Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.

Tafamidis is a selective stabilizer for transthyretin （TTR）， used for the treatment of transthyretin amyloidosis with cardiomyopathy （ATTR-CM） and transthyretin amyloidosis with polyneuropathy （ATTR-PN）. This article provides a review of the basic information and clinical studies on the efficacy and safety of tafamidis. It is found that tafamidis slows down or prevents the progression of TTR amyloidosis by inhibiting the dissociation of TTR tetramers. Multiple clinical studies have shown that tafamidis has good efficacy and safety， significantly reducing all-cause mortality and cardiovascular-related hospitalization rates in patients with amyloidosis， and delaying disease progression. Although tafamidis treatment may have certain limitations， it is still a key drug for the treatment of TTR amyloidosis， and the first drug approved for the treatment of ATTR-CM.