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.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

OBJECTIVE To investigate the expression and prognosis of SDHB gene in pan-cancer by bioinformatics analysis,and to explore SDHB-related genes,potential pathways and immune cell infiltration in pheochromocytoma paraganglioma(PPGL).METHODS The expression of SDHB gene in pan-cancer and its relationship with survival prognosis were analyzed in The Cancer Genome Atlas(TCGA)and genotype-tissue expression(GTEx)databases.The expression changes of other genes affected by SDHB mutations,the enrichment analysis and signaling pathway analysis in PPGL patients were carried out by analyzing the TCGA database and the TARGET database.In addition,the relationship between SDHB expression and immune cell infiltration in PPGL patients was explored.RESULTS Compared with normal tissues,the expression of SDHB in 21 tumors was higher than that in normal tissues(P<0.01):BLCA,BRCA,CESC,COAD,DLBC,ESCA,GBM,HNSCC,LGG,LUAD,LUSC,OV,PAAD,PRAD,READ,SKCM,STAD,THCA,THYM,UCEC and UCS.It was expressed lower than normal in 7 other tumors(P<0.01),including ACC,CHOL,KICH,KIRC,KIRP,LAML and PPGL.The relationship between SDHB expression and survival prognosis was analyzed,and it was found that in STAD,KIRC,MESO,OS,and KIR,lower SDHB expression predicted poor prognosis,while higher expression predicted good prognosis.In UCEC,LGG,HNSCC,LAML,OSCC,and ACC,lower SDHB expression predicted a better prognosis,and similarly,higher expression predicted a poor prognosis.In correlation and enrichment analysis,the expression of SDHB was mainly related to neuroactive ligand-receptor interaction,Cushing's syndrome,cortisol synthesis and secretion,peptide receptor activity,G protein-coupled peptide receptor activity,neuropeptide receptor activity,intrinsic components of the synaptic membrane,components of the synaptic membrane,components of the postsynaptic specialized membrane,cyclic nucleotide-mediated signaling pathways,neuropeptide signaling pathways,glucocorticoid metabolism processes and other signaling pathways.In immune infiltration analysis,it was found that the immune cells with the highest infiltration in the SDHB lower expression group were pDC cells and TReg cells,suggesting that pDC cells and TReg cells may play a certain role in PPGL patients.CONCLUSION SDHB gene is abnormally expressed in a variety of tumors,and it has a certain correlation with the prognosis of tumors.In PPGL patients,the signaling pathways affected by SDHB and highly infiltrating immune cells provide new insights for future mechanistic studies and immunotherapy.

Objective To compare the effects of two different surgical methods in the treatment of female unilateral cT1N0-1a thyroid cancer and the satisfaction of incision cosmetics.Methods A retrospective analysis of the data of female patients with unilateral cT1N0-1a stage thyroid cancer in our hospital from October 2020 to September 2022 was conducted.They were divided into open group(65 cases)and oral group(55 cases)according to different surgical methods.Patients in open group were underwent traditional open thyroid surgery,and patients in oral group were underwent transoral vestibular approach laparoscopic thyroid surgery.Intraoperative conditions,postoperative complications and satisfaction degree of postoperative incision beauty between the two groups were comparded.Results The operation time was(124.40±11.59)minutes and the dissection time of the central lymph node was(26.44±5.33)minutes in the transoral group,which were longer than those in the open group[(65.91 ±11.44)minutes and(17.38±4.32)minutes,(P＜0.05)].Vancouver scar evaluation[(3.29± 0.96)points],patient scar evaluation[(8.62±1.57)points],observer scar evaluation[(6.67±1.17)points]and scar self-awareness score[(1.65±0.70)points]in the oral group were significantly lower than those in the open group[(5.29±1.20)points,(15.02±2.85)points,(19.57±2.94)points and(3.12±0.98)points,(P＜0.05)].There were no significant difference in the amount of blood loss,the amount of drainage,the number of days in hospital and the number of central lymph nodes dissection between the two groups(P＞0.05).There was no significant difference in total incidence of postoperative complications(hoarseness,cough after drinking water,postoperative bleeding,subcutaneous effusion)between oral group and open group(7.2％vs7.6％,P＞0.05).Conclusion The two surgical methods have their own advantages,the incidence of postoperative complications is low,safe and reliable,and the patients in the oral group are more satisfied with the cosmetology of the postoperative incision.In actual clinical work,the appropriate operation can be chosen according to the specific conditions of the patients.

Objective:To investigate the application effect of bullet screen interaction in the teaching of internal medicine of traditional Chinese medicine.Methods:A randomized controlled trial was conducted, and 150 students were randomly divided into bullet screen interaction group and traditional interaction group and received teaching with bullet screen interaction and traditional interaction, respectively. Flanders Interaction Analysis System (FIAS), class rating, questionnaire survey, and performance test were used to evaluate the effect of classroom interaction and teaching achievement. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:Compared with the traditional interaction group, the bullet screen interaction group had a significantly lower teacher's language ratio [(62.63±2.83)% vs. (71.05±3.19)%] and significantly higher student's language ratio [(32.68±2.62)% vs. (22.79±1.32)%], teacher's indirect/direct influence ratio [(96.63±9.59)% vs. (69.84±3.48)%], and teacher's positive/negative influence ratio [(122.89±6.43)% vs. (50.58±2.35)%]. Compared with the traditional interaction group, the bullet screen interaction group had significantly higher scores of teacher's emotional atmosphere (23.82±6.54 vs. 21.01±6.51), quality of classroom activities (25.67±5.51 vs. 22.56±11.95), and information transmission of teacher's classroom interactive activities (25.46±10.30 vs. 18.44±6.52). The questionnaire survey showed that compared with the traditional interaction group, the bullet screen interaction group had a significantly higher number of the students who selected excellent and good for student interest in classroom, dullness of classroom, and the mastery of classroom knowledge [104 (69.33%)/110 (73.33%)/106 (70.67%) vs. 72(48.00%)/74 (49.33%)/84(56.00%)], and the bullet screen interaction group had significantly higher scores of basic knowledge and case analysis than the traditional interaction group (84.30±4.13/78.53±7.21 vs. 79.26±5.67/72.56±4.22).Conclusions:The application of bullet screen interaction teaching in the teaching of internal medicine of traditional Chinese medicine can help to improve interactive effect and teaching achievement.

Objective:To observe the in vivo microscopic histological changes during the treatment of melasma using reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT), and to explore its application value in evaluating therapeutic efficacy. Methods:Clinical data were collected from 30 melasma patients treated at the Department of Dermatology, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, from January to October 2023. Retrospective analyses were performed on clinical photographs taken before treatment and at weeks 4, 8, 12, and 16 after the start of treatment, and the efficacy was evaluated by using the melasma area and severity index (MASI) scores. Meanwhile, changes in RCM imaging indicators, such as pigment distribution patterns, melanocyte morphology and spatial distribution patterns, and inflammatory infiltration in the superficial dermis in melasma lesions, were retrospectively analyzed. For clear elucidation of concepts and subsequent quantitative analysis, characteristic microscopic histological changes in melasma lesions before treatment were classified into several patterns based on RCM findings and previous literature reports. Additionally, optical coherence signals collected by OCT were used to asses characteristic vessel parameters in the lesions before and after treatment. Finally, correlations between various microscopic histological changes and clinical efficacy were analyzed using Spearman's correlation analysis.Results:With the increase in treatment duration, the proportions of pigment distribution patterns Ⅱ and Ⅲ observed by RCM gradually decreased, while the proportion of the nearly normal pattern Ⅰ markedly increased; the proportions of the 4 heterogeneous morphological patterns of melanocytes all decreased, while the pattern Ⅱ melanocytes were still focally distributed in the lesions at the last time of observation; meanwhile, the proportions of melanocyte spatial distribution patterns Ⅱ and Ⅲ decreased, which gradually restored to the normal pattern Ⅰ; the infiltration of melanophages and inflammatory cells in the superficial dermis diminished, and the proportion of the pattern Ⅲ inflammatory infiltration markedly decreased at week 4, but it lasted for a long time. The decrease rate of MASI scores was significantly correlated with the decrease rate of the proportions of pigment distribution patterns Ⅱ and Ⅲ ( r = 0.82, 0.97, respectively, both P < 0.05), melanocyte morphological patterns Ⅰ, Ⅲ, and Ⅳ ( r = 0.84, 0.83, 0.83, respectively, all P < 0.05), and inflammatory infiltration patterns Ⅰ and Ⅲ ( r = 0.85, 0.81, respectively, both P < 0.05), as well as the increase rate of the proportion of melanocyte spatial distribution pattern Ⅰ ( r = 0.89, P < 0.05), indicating that these indicators can be sensitive evaluation indicators for clinical efficacy. Moreover, OCT revealed a decrease in the average diameter and density of vessels in the lesions after treatment, and the decrease rates were correlated with the decrease rate of MASI scores ( r = 0.76, 0.78, respectively, both P < 0.05) ; there was no significant difference between the pre- and post-treatment average depth of vascular plexuses. Conclusion:During the treatment of melasma, RCM combined with OCT could serve as a non-invasive approach with objective and robust evidence for evaluating the therapeutic efficacy.

Objective To investigate the active ingredients and components that inhibiting cathepsin K activity in Erzhi Wan, a classic kidney-tonifying formula. Methods Then-butanol, dichloromethane, ethyl acetate and petroleum ether parts and 30 active components in Erzhi Wan were screened by established high throughput fluorescence methods of inhibit the binding activity of CTSK with Z-FR-MCA substrate, the formation of CTSK and chondroitin sulfate A (CSA) complex activity, and the activity of substrate type I collagen degradation by CTSK. Molecular docking and insoluble collagen substrate binding assays were applied to verify the potential CTSK inhibitors. Results The n-butanol and petroleum ether parts of Erzhi Wan inhibited the formation of CTSK and CSA^* complex by more than 90%, the petroleum ether part inhibited the binding of CTSK to substrate Z-FR-MCA by more than 90%, the collagen degradation inhibition rate of CTSK in n-butanol part was more than 95% and that in petroleum ether part was 58.6%. Among the 30 active components, 11 showed that the inhibition rate of CTSK and CSA^* complex formation was more than 50%, and 5 components with the inhibition rate of Z-FR-MCA binding activity more than 50%. Finally, there were four components including eclalbasaponin Ⅸ, (-)-epicatechin gallate, nuezhenoside and wedelolactone. The inhibition rate of collagen degradation was more than 50%. Eclipta saponin IX inhibited the binding rate between collagen fibers and CTSK, up to 60%, but all of them failed to dock with CTSK active site. Conclusion There are active components that inhibiting cathepsin K in Erzhi Wan, which mainly exists in the n-butanol ingredients, but the active components is not an active-site inhibitor. It might inhibit the binding of CTSK with oligosaccharides by binding to other sites of CTSK, and then reduce the collagen degradation activity of CTSK.

Objective:To explore the feasibility of cardiac T 2 weighted dark blood sequence (T 2W-DB) based on artificial intelligence assisted compression-sensing(ACS) in clinical cardiac MR examination, compared with the conventional cardiac fast spin-echo T 2W-DB sequence. Methods:A total of 38 patients referred for cardiac MR examination in Tongji Hospital were enrolled prospectively from August to December 2021. The conventional T 2W-DB scan and the single-shot ACS T 2W-DB scan were acquired at continuous short-axial slices covering the whole left ventricle in all patients, and the acquisition time of each scan was recorded. The image quality of the two sequences was evaluated by the objective quantitative parameters and the subjective scoring methods, respectively. The signal to noise ratio (SNR), the contrast to noise ratio of the interventricular septum to blood pool (CNR), and the sharpness of the images were calculated. The subjective scoring was to evaluate the overall image quality, the effect of blood pool suppression, the visibility of right ventricular free wall, left ventricular free wall, and interventricular septum with a 5-point Likert scale. The intraclass correlation coefficient and Kendall W were calculated to evaluate the interobserver agreement of the objective quantitative parameters and subjective scoring. The paired t-test or Wilcoxon test was used to compare the difference in acquisition time, objective quantitative parameters and subjective scoring between the conventional T 2W-DB and the single-shot ACS T 2W-DB. Results:The inter-observer agreement between the single-shot ACS T 2W-DB and conventional T 2W-DB was good in all the objective quantitative parameters and subjective scoring of image quality ( P<0.05 for all). Compared with conventional T 2W-DB, acquisition time of single-shot ACS T 2W-DB was remarkably shortened [(85.8±14.7) s vs. (16.9±3.0) s, t=35.42, P<0.001]. Compared with SNR (66.4±29.0) and CNR(61.8±28.6) of conventional T 2W-DB, single-shot ACS T 2W-DB had significantly higher SNR(110.8±36.8, t=-8.13, P?0.001) and CNR(88.2±31.1, t=-5.89, P?0.001). Compared with conventional T 2W-DB, single-shot ACS T 2W-DB had better blood pool inhibition effect (4.6±0.6 vs. 4.7±0.5, Z=-2.64, P=0.008). There was no significant difference in overall image quality, visibility of right ventricular free wall, left ventricular free wall, and interventricular septum between the two sequences( P>0.05 for all). Conclusions:In cardiac MR examination, compared with the conventional T 2W-DB sequence, the single-shot ACS T 2W-DB sequence can significantly shorten the acquisition time and obtain better image quality.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

BACKGROUND: Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. METHODS: Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. RESULTS: During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively. CONCLUSIONS High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.