Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.

Metagenomic analyses of humans and animals have showed that atopic dermatitis (AD) is associated with microbiome dysbiosis in the gut and skin. Decrease of microbial diversity can cause damage to skin barrier and aggravation of AD, and gut microbiome may be involved in the occurrence and development of AD through immune, metabolic and neuroendocrine pathways. This review summarizes the latest advances in the application of metagenomics in tmicrobiological research in and treatment of AD, possible mechanisms underlying microbiome-mediated pathogenesis of AD, and provides a theoretical reference for the microecological therapy of AD.

Objective: To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis (AD) , and to elucidate their roles in the pathogenesis of AD. Methods: From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues. Results: An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21 729 genes were detected, including 19 268 known genes and 2 545 predicted novel genes. A total of 23 153 new transcripts were detected, of which 18 889 were new alternative splicing subtypes of known protein-coding genes, 2 545 were transcripts belonging to new protein-coding genes, and the remaining 1 719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20) . GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin (IL) -17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results. Conclusions Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD..

To evaluate the estimation of prevalence ratio (PR) by using bayesian log-binomial regression model and its application,we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software.The results showed that caregivers' recognition of infant's risk signs of diarrhea was associated significantly with a 13％ increase of medical care-seeking.Meanwhile,we compared the differences in PR's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1:not adjusting for the covariates;model 2:adjusting for duration of caregivers' education,model 3:adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model.The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95％CI:1.005-1.265),1.128(95％CI:1.001-1.264)and 1.132(95％CI:1.004-1.267),respectively.Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95％ CI:1.055-1.206) and 1.126(95％ CI:1.051-1.203),respectively,but the model 3 was misconvergence,so COPY method was used to estimate PR,which was 1.125 (95％CI:1.051-1.200).In addition,the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model,but they had a good consistency in estimating PR.Therefore,bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

OBJECTIVE: To evaluate the application of flaps or musculocutaneous flaps in repairing cervical postradiation ulcer (cpu) at nasopharyngeal carcinoma. METHOD: Deltopectoral flaps and pectoralis major flaps were applied to repair cervical radiation ulceration with different size and depth in 19 cases. RESULT: Twelve cases repaired with deltopectoral flaps and 7 cases repaired with pectoralis major flaps, impaired wound healing happened at distal end of one deltopectoral flap, and the wound was healing hy second intention after debridement and dressing change. All the other deltopectoral flaps and pectoralis major flaps stayed alive. Flaps stayed alive without the recurrence of ulcer after the long-term follow-up for one to ten years. CONCLUSION The effectiveness of cervical radiation ulceration reconstruction by deltopectoral flaps and pectoralis major flaps was proved. The reconstruction could prevent the recurrence of ulcer. Refer to the poor prognosis of chronic radiation ulceration with expectant treatment, precautions do count.
Adult ; Aged ; Carcinoma ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; radiotherapy ; Neck ; Radiation Injuries ; etiology ; surgery ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Surgical Flaps

Objective To analyze the efficacy and cosmetic results of intensity modulate radiation therapy (IMRT) for breast cancer after breast-conserving surgery.Methods From 2003 to 2006, 117 patients with breast cancer, after breast-conserving surgery followed by 4 - 6 cycles of chemotherapy,received intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT).The radiation dose was 50 Gy in 25 fractions to the whole breast and 10 Gy boost to the tumor bed.Patients with positive hormone receptors then received endocrine treatment.Results The follow-up rate was 94.0% until September 2009.114 and 91 patients were followed up to 3 and 5 years, respectively.The 3-and 5-year overall survival rates were 99.1% and 96%.The 5-year disease free survival and local recurrence rates were 88% and 3.6%.Cosmetic results were satisfied.Severe radiation toxicities, such as radiation pneumonitis, pulmonary fibrosis and heart injury were not found.Conclusions Patients treated with IMRT after breast-conserving surgery have a satisfied prognosis as well as cosmetic results.

OBJECTIVE: To detect and analyze the EBV-LMP1 gene N terminus XhoI-site mutation and C terminus 30 bp deletion in plasma of patients with nasopharyngeal carcinoma (NPC) in Chongqing of China. METHOD: DNA extraction and PCR amplification was used in plasma of 48 NPC patients and 40 control non-NPC cases from Chongqing of China. All the PCR production of N terminus was digested by enzyme XhoI, then segregated in 8% PAGE. All- the PCR production of C terminus was segregated in 8% PAGE too. Compared with B95-8 cell, some of the PCR production were sequenced and analyzed with software. RESULT: LMP1 was amplified successfully from 48 of 48 NPC cases (100%) and from 38 of 40 non-NPC cases (95%) by PCR, but none of LMP1 XhoI-site mutation and none of 30 bp deletion was found by digesting, segregating and Sequencing. CONCLUSION EBV-LMP1 gene N terminus XhoI-site and C terminus 30 bp deletion have no mutation in plasma of NPC or non-NPC cases in Chongqing of China. The precise relationship of EBV-LMP1 gene mutation or deletion with NPC pathogenesis needs further investigation.
Adult ; China ; DNA, Viral ; genetics ; Female ; Herpesvirus 4, Human ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; genetics ; pathology ; virology ; Sequence Deletion ; Viral Matrix Proteins ; blood ; genetics

A strain of Prototheca species isolated from a case of meningitis was identified by routine morphologic and biochemical methods as well as amplification of the related genes, in which the 28S large-subunit (LSU) region of ribosomal RNA (rRNA) gene and intergenic space (ITS) were amplified with universal fungal primers. The small-subunit (SSU) rRNA gene was amplified with eukaryote-specific primers and Prototheca genus-specific primers. Then, compared the sequences with the ones posted on BLAST (www. ncbi. nlm. nih. gov/BLAST). The organism choice giving the closest match, up to 99%, was considered the most likely correct identification. It was found that this strain of fungus grew well at 25 ℃ or 37 ℃. Smooth,moist colonies with white color were observed on Sabouraud Dextrose Agar (SDA) and Potato Dextrose Agar (PDA). Microscopically, globular or ovoid cells, a number of round, ovoid shaped endospores could be observed. No hypha, ascus or blastic conidia was found upon cultivation on SDA. Based on the morphological characteristics, this isolate could be identified as Prototheca species. The identity with Prototheca wickerhamii was 2.9 % as demonstrated by the API 20C AUX system. Sequence analysis showed that the ITS gene was proved to be a complex structural region which was not suitable for the identification of Prototheca species, but the LSU and SSU rDNA regions showed 94% and 99.9% sequence identities with Prototheca zopfii var. hydrocarbonea (P. zopfii var. hydrocarbonea) respectively, indicating that the SSU rRNA gene sequence might be more reliable on than the LSU rRNA gene sequence for identification of Prototheca species.