Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the effects of external application of Sanying Plaster on the size of thyroid nodules and the states of depression and anxiety in patients with benign thyroid nodules.Methods:A randomized controlled trial was conducted. A total of 120 patients with benign thyroid nodules from the outpatient clinic of the Department of Thyroid Diseases at Shanghai Traditional Chinese Medicine Hospital from June to December 2022 were selected as the subjects of the study. They were divided into two groups using the random number table method, with 60 patients in each group. The control group received lifestyle intervention treatment, while the treatment group received Sanying Ointment in addition to the treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were measured before and after treatment; the maximum diameter of thyroid nodules was measured using a color Doppler ultrasound transverse section; the quality of life was assessed using the short form 36 (SF-36); the degree of anxiety and depression was evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS); adverse reactions during the treatment period were recorded, and the clinical efficacy was evaluated.Results:During the treatment period, 4 cases in the treatment group and 3 cases in the control group did not complete the treatment. Finally, 56 cases in the treatment group and 57 cases in the control group entered the efficacy evaluation. The total effective rate of the treatment group was 71.4% (40/56), and that of the control group was 14.0% (8/57), with a statistically significant difference between the two groups ( χ2=26.82, P<0.001). After treatment, the TCM syndrome score of the treatment group (10.02±3.65 vs. 16.65±3.44, t=-10.24) was lower than that of the control group ( P<0.001); the maximum diameter of thyroid nodules [11.00 (4.65, 19.93) mm vs. 15.00 (7.15, 28.50) mm, Z=-2.43] was lower than that of the control group ( P<0.05); the SF-36 score [121.83 (117.00, 130.00) vs. 114.42 (104.25, 127.50), Z=-2.62] was higher than that of the control group ( P<0.01); the SDS (46.72±4.59 vs. 57.02±5.99, t=14.80) and SAS (42.25±5.72 vs. 50.60±7.12, t=10.04) scores were lower than those in the control group ( P<0.001). The incidence of adverse reactions during the treatment period in the treatment group was 3.5% (2/57), and no adverse reactions occurred in the control group. Conclusion:The external application of Sanying Ointment helps to reduce the size of thyroid nodules in patients with benign thyroid nodules, improve the quality of life and anxiety and depression, and increase clinical efficacy with good safety.

Objective To analyze the effects of GATA binding protein 3(GATA3)mediated mini RNA-21(miR-21)/phosphatase and tensin homologue(PTEN)axis missing from human chromosome Chromosome 10 on the proliferation and invasion of endometrial cancer cells.Methods HEC-1-A cells were transfected and divided into control group,GATA3 empty plasmid group,GATA3 overexpression plasmid group,GATA3 siRNA negative control group,and GATA3 siRNA group.Detect the expression levels of GATA3,miR-21,PTEN,proliferation,apoptosis rate,migration,and invasion in each group of cells.Results Compared with the hEEC group,the expression levels of GATA3 and miR-21 in cells of the HEC-1-A group,HEC-1-B group,and Ishikawa group increased,while the expression levels of PTEN decreased(P<0.05).Compared with the GATA3 empty plasmid group,the GATA3 overexpression plasmid group showed an increase in GATA3,miR-21 mRNA expression,pro-liferation rate,migration distance,number of invading cells,and Vimentin levels,while the PTEN mRNA expression,apoptosis rate,Caspase-9,Bax,and E-cadherin levels decreased(P<0.05);Compared with the GATA3 siRNA negative control group,the GATA3,miR-21 mRNA expression,proliferation rate,migration distance,number of invading cells,and Vimentin level decreased,while the PTEN mRNA expression,apoptosis rate,Caspase-9,Bax,and E-cadherin levels increased(P<0.05).Conclusion Downregulation of GATA3 expression can regulate the miR-21/PTEN axis,slow down the proliferation of HEC-1-A cells,and promote apoptosis of HEC-1-A cells.

Objective:To investigate the chain mediating role of psychological resilience and coping styles between social support and psychological distress in elderly stroke patients.Methods:Using convenience sampling, 245 elderly stroke patients with their first episode, admitted to the Neurology Department of the Affiliated Hospital of Hebei University from June to July 2023, were recruited as study subjects. A questionnaire survey was conducted using a General Information Questionnaire, Distress Thermometer for Stroke Patients, Perceived Social Support Scale, Connor-Davidson Resilience Scale Short Form, and Medical Coping Modes Questionnaire. Pearson correlation analysis was used to examine the relationships between psychological distress, social support, psychological resilience, and coping styles in elderly stroke patients. Harman's single-factor test was employed to detect common method bias among variables. The PROCESS macro in SPSS software was utilized to test the chain mediation effects.Results:A total of 245 questionnaires were distributed, with 230 valid responses collected, yielding a response rate of 93.9%. Among the 230 elderly stroke patients, the incidence of psychological distress was 23.9% (55/230). Significant correlations were observed among psychological distress, social support, psychological resilience, and coping styles ( P<0.05). Social support influenced psychological distress through the mediation of psychological resilience and confrontational coping, with a total indirect effect of -0.098. The same relationship existed for social support through psychological resilience and avoidant coping, with a total indirect effect of -0.058. Additionally, social support influenced psychological distress through psychological resilience and submissive coping, with a total indirect effect of -0.113. Avoidant coping had a suppressing effect on the influence of social support on psychological distress. Conclusions:Elderly stroke patients experienced moderate to low levels of psychological distress. Psychological resilience and coping styles played a chain-mediating role between social support and psychological distress. Special attention should be given to elderly stroke patients with low levels of social support.

Objective:To determine the expression of adenylate cyclase genes ADCY2/4/5/8 in cutaneous melanoma, to explore their roles and mechanisms of action, and to verify their effect on the proliferation and migration of the melanoma cell line A375.Methods:Data on the mRNA and protein expression of ADCY2/4/5/8, as well as the correlation between gene expression and prognosis, were analyzed through the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases; ADCY2/4/5/8 gene methylation and mutation status were analyzed through the UALCAN, DeMth, and cBioPortal databases; Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the ADCY2/4/5/8 genes using the DAVID and STRING databases. qPCR was conducted to determine the relative mRNA expression of ADCY2/4/5/8 in the A375 melanoma cells and FF pigmented nevus cells. Cultured A375 cells were divided into experimental groups and control groups to be transfected with ADCY2/4/5/8 overexpression plasmids and empty vectors, respectively. Cell counting kit (CCK8) and Transwell assays were performed to evaluate the effect of ADCY2/4/5/8 overexpression on the proliferation and migration of A375 cells, qPCR was conducted to determine the relative mRNA expression of genes related to the proliferation and migration of A375 cells, and Western blot analysis to determine the expression of cyclic adenosine monophosphate (cAMP) signaling pathway-related proteins in A375 cells after the overexpression of ADCY2/4/5/8. One-way analysis of variance and repeated measures analysis of variance were used for the comparison among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:Bioinformatics analysis based on the GEPIA database showed that the mRNA expression of ADCY2, ADCY4, ADCY5, and ADCY8 was down-regulated in melanoma tissues ( n = 461) compared with normal tissues ( n = 558, P < 0.01) ; stratified analysis showed that the mRNA expression of ADCY2 ( P = 0.015) and ADCY8 ( P = 0.038) was correlated with tumor staging, and the lower the mRNA expression, the later the tumor stage. In the HPA database, the ADCY2/4/5/8 protein expression was reduced in 30 melanoma tissues compared with 30 normal tissues ( P < 0.001). Analysis of the UALCAN and DeMth database data showed elevated methylation levels of ADCY2/4/5/8 in melanoma tissues and metastatic melanoma tissues compared with normal tissues ( P < 0.001). Analysis of the DAVID and STRING database data demonstrated that the ADCY2/4/5/8 gene may inhibit cell proliferation and migration by activating the cAMP signaling pathway. qPCR showed that the relative mRNA expression of ADCY2/4/5/8 was lower in A375 cells than in FF cells. CCK8 assay showed that the survival rates of A375 cells were significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups at 48 and 72 hours (all P < 0.05). Transwell assay showed that the number of migratory A375 cells was significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.01). As qPCR revealed, the ADCY2/4/5/8 overexpression groups showed significantly upregulated relative mRNA expression of epithelial cadherin, but significantly downregulated relative mRNA expression of Ki67, vimentin, neural cadherin, and matrix metalloproteinase 2 compared with the corresponding control groups (all P < 0.001). Western blot analysis showed that the protein expression of cAMP and phosphorylated protein kinase A (p-PKA) in A375 cells was significantly higher in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.001), but there were no significant differences in the PKA protein expression levels between the ADCY2/4/5/8 overexpression groups and the corresponding control groups (all P > 0.05) . Conclusion:The expression of ADCY2/4/5/8 was downregulated in melanoma tissues, and overexpressed ADCY2/4/5/8 could inhibit the proliferation and migration of melanoma cells, suggesting that ADCY2/4/5/8 may serve as potential tumor suppressor genes in the progression of melanoma.

Objective To explore the diagnostic value of deep medullary vein (DMV) score for cognitive impairment in patients with cerebral small vessel disease (CSVD).Methods Collect clinical and imaging data of 108 patients who visited Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from May 2022 to December 2023.According to the mini-mental state examination,patients were divided into a cognitive impairment group (36 cases) and a cognitive function normal group (72 cases).On magnetic sensitive images,the DMV scores of the six regions on both sides of the frontal lobe,parietal lobe,occipital lobe are rated from 0 to 3 points based on their visual conditions,and the total scores of the six regions is the DMV score (0 to 18 points).Applying international CSVD guidelines to assess CSVD burden in patients.Analyze the correlation between DMV score and cognitive impairment,and compare the diagnostic value of DMV scores and CSVD score for cognitive impairment.Results The median CSVD burden score of 108 patients was 1 (0,2) points,and the median DMV score was 4 (1,9) points.The DMV score was positively correlated with the presence of cognitive impairment (r=0.525,P<0.001).There were statistically significant differences in age,cerebral microbleeds,perivascular space enlargement,white matter hyperintensities,CSVD burden,and DMV score between the cognitive impairment group and the cognitive function normal group (P<0.05).The area under the receiver operating characteristic curve of diagnosed with cognitive impairment using DMV score was 0.820 (95％CI:0.741-0.898,P<0.001).Conclusion DMV score is positively correlated with CSVD cognitive impairment,and it has certain predictive value for cognitive impairment.

Objective: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM. Methods: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM. Results: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61–0.70), 0.72 (95% CI, 0.62–0.70), and 0.70 (95% CI, 0.61–0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort. Conclusion We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.

Objective: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM. Methods: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM. Results: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61–0.70), 0.72 (95% CI, 0.62–0.70), and 0.70 (95% CI, 0.61–0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort. Conclusion We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.

Objective: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM. Methods: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM. Results: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61–0.70), 0.72 (95% CI, 0.62–0.70), and 0.70 (95% CI, 0.61–0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort. Conclusion We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.

Objective: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM. Methods: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM. Results: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61–0.70), 0.72 (95% CI, 0.62–0.70), and 0.70 (95% CI, 0.61–0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort. Conclusion We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.