1. Progress and prospect of inhaled biological agents in asthma
Guanghui LI ; Jing HUANG ; Min ZHU ; Yakun WAN ; Zhihong CHEN ; Rui ZHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(4):406-414
More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.
2.Reliability of Pod Shape Diagram from Caloric Test in Vertigo Patients
Shujing LI ; Donghai WANG ; Yu WANG ; Yi DU ; Xingjian LIU ; Lili REN ; Ziming WU
Journal of Audiology and Speech Pathology 2024;32(1):6-10
Objective To understand the reliability of caloric test results through the analysis of the pod shape dia-gram types of caloric test and to provide a more accurate and reliable basis for vestibular system function evaluation.Meth-ods The results of caloric test in 528 patients from July 2021 to May 2022 in vertigo diagnosis and treatment center were analyzed.According to pod pattern and unilateral weakness(UW),the patients were divided into five groups:cold and warm test symmetrical group,left and right side asymmetry group,single value significant abnormal group,bilateral hypo-plasia group and pod morphology unable to be classified group.Unreliable data can be identified by comparing,explaining,and summarizing the results of UW of different groups,so as to reduce the interference of unreliable data to clinical diagno-sis and treatment.Results Cold and warm test symmetric group(n=439)included patients with symmetry of bilateral vestibular function(n=273)and decreased vestibular function of one side(n=166).Left and right symmetrical groups in-eluded pationts with bilateral symmetric vestibular function(n=11)and unilateral reduction(n=13).Single value signifi-cant abnormal group showed cases with unilateral vestibular function reduction(n=25)and bilateral symmetric vestibular function(n=11).Bilateral hypolasion group showed cases with bilateral symmetric vestibular function(n=25)and unilat-eral reduction(n=9).Pod morphology unclassified group(n=5)suggested varions interference factors.Conduson When the function of the peripheral vestibular is symmetrical and normal,we should be alert to the existence of temperature effect,and should consider the inspection of the perfusion apparatus and the calibration of the irrigation temperature.When the function of the peripheral vestibular shows unilateral weakness,repeating the irrigation is recommended when the single value of the caloric test significantly increases or decreases.If there is no change,repeating the irrigation at the same tem-perature in the other ear or even repeating the whole caloric test are recommended.The UW value could not truly reflect the state of peripheral vestibular function when the caoric test produces bilateral weakness.Therefore,water irrigation could be used to make a correct judgment based on the medical history and other auxiliary examinations.It is of great significance to judge the effectiveness of caloric test comprehensively by combining the morphology of pod diagram with UW value.
3.Predictors of Difficult Laryngeal Exposure in Suspension Laryngoscopy: A Systematic Review and Meta-Analysis
Mengshu WANG ; Yong LIU ; Yuanzheng QIU ; Huihong CHEN ; Wang LIWEN ; Donghai HUANG ; Xin ZHANG ; Guo LI
Clinical and Experimental Otorhinolaryngology 2024;17(2):177-187
Objectives:
. Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system.
Methods:
. We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables.
Results:
. The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48).
Conclusion
. We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.
4.The Porous SilMA Hydrogel Scaffolds Carrying Dual-Sensitive Paclitaxel Nanoparticles Promote Neuronal Differentiation for Spinal Cord Injury Repair
Zhixiang LI ; Tao ZHOU ; Zhengqi BAO ; Min WU ; Yingji MAO
Tissue Engineering and Regenerative Medicine 2024;21(6):809-827
BACKGROUND:
In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair.
METHODS:
In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair.
RESULTS:
The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs.
CONCLUSION
The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.
5.Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023)
Zeli ZHANG ; Shoujia SUN ; Yijun BAO ; Li BIE ; Yunxing CAO ; Yangong CHAO ; Juxiang CHEN ; Wenhua FANG ; Guang FENG ; Lei FENG ; Junfeng FENG ; Liang GAO ; Bingsha HAN ; Ping HAN ; Chenggong HU ; Jin HU ; Rong HU ; Wei HE ; Lijun HOU ; Xianjian HUANG ; Jiyao JIANG ; Rongcai JIANG ; Lihong LI ; Xiaopeng LI ; Jinfang LIU ; Jie LIU ; Shengqing LYU ; Binghui QIU ; Xizhou SUN ; Xiaochuan SUN ; Hengli TIAN ; Ye TIAN ; Ke WANG ; Ning WANG ; Xinjun WANG ; Donghai WANG ; Yuhai WANG ; Jianjun WANG ; Xingong WANG ; Junji WEI ; Feng XU ; Min XU ; Can YAN ; Wei YAN ; Xiaofeng YANG ; Chaohua YANG ; Rui ZHANG ; Yongming ZHANG ; Di ZHAO ; Jianxin ZHU ; Guoyi GAO ; Qibing HUANG
Chinese Journal of Trauma 2023;39(3):193-203
The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.
6.Identification of biomarkers in laryngeal cancer by weighted gene co-expression network analysis.
Fengyu ZHANG ; Li SHE ; Donghai HUANG
Journal of Central South University(Medical Sciences) 2023;48(8):1136-1151
OBJECTIVES:
Laryngeal cancer (LC) is a globally prevalent and highly lethal tumor. Despite extensive efforts, the underlying mechanisms of LC remain inadequately understood. This study aims to conduct an innovative bioinformatic analysis to identify hub genes that could potentially serve as biomarkers or therapeutic targets in LC.
METHODS:
We acquired a dataset consisting of 117 LC patient samples, 16 746 LC gene RNA sequencing data points, and 9 clinical features from the Cancer Genome Atlas (TCGA) database in the United States. We employed weighted gene co-expression network analysis (WGCNA) to construct multiple co-expression gene modules. Subsequently, we assessed the correlations between these co-expression modules and clinical features to validate their associations. We also explored the interplay between modules to identify pivotal genes within disease pathways. Finally, we used the Kaplan-Meier plotter to validate the correlation between enriched genes and LC prognosis.
RESULTS:
WGCNA analysis led to the creation of a total of 16 co-expression gene modules related to LC. Four of these modules (designated as the yellow, magenta, black, and brown modules) exhibited significant correlations with 3 clinical features: The age of initial pathological diagnosis, cancer status, and pathological N stage. Specifically, the yellow and magenta gene modules displayed negative correlations with the age of pathological diagnosis (r=-0.23, P<0.05; r=-0.33, P<0.05), while the black and brown gene modules demonstrated negative associations with cancer status (r=-0.39, P<0.05; r=-0.50, P<0.05). The brown gene module displayed a positive correlation with pathological N stage. Gene Ontology (GO) enrichment analysis identified 77 items, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 30 related signaling pathways, including the calcium signaling pathway, cytokine-cytokine receptor interaction, neuro active ligand-receptor interaction, and regulation of lipolysis in adipocytes, etc. Consequently, central genes within these modules that were significantly linked to the overall survival rate of LC patients were identified. Central genes included CHRNB4, FOXL2, KCNG1, LOC440173, ADAMTS15, BMP2, FAP, and KIAA1644.
CONCLUSIONS
This study, utilizing WGCNA and subsequent validation, pinpointed 8 genes with potential as gene biomarkers for LC. These findings offer valuable references for the clinical diagnosis, prognosis, and treatment of LC.
Humans
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Laryngeal Neoplasms/genetics*
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Rosaniline Dyes
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Biomarkers
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Adipocytes
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Gene Regulatory Networks
;
Gene Expression Profiling
7.Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.
Dandong FANG ; Yu LI ; Bo HE ; Daqian GU ; Mingming ZHANG ; Jingwen GUO ; Hongmei REN ; Xinyue LI ; Ziyue ZHANG ; Ming TANG ; Xingbing LI ; Donghai YANG ; Chunmei XU ; Yijie HU ; Hongyong WANG ; Pedro A JOSE ; Yu HAN ; Chunyu ZENG
Acta Pharmaceutica Sinica B 2023;13(9):3756-3769
Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.
8.Progress of CDK4/6 inhibitors in treatment of hormone receptor-positive and human epithelial growth factor receptor 2-negative breast cancer
Xin LI ; Huayi ZHANG ; Donghai LI ; Le WANG ; Kailin YANG ; Gang GUO
Cancer Research and Clinic 2023;35(9):713-716
Cyclin-dependent kinase (CDK)4/6 inhibitors combined with traditional endocrine therapy can significantly improve the progression-free survival and overall survival of hormone receptor-positive and human epithelial growth factor receptor 2-negative breast cancer patients. But different drugs, dosage and medication cycle will also bring different efficacy and safety incidents to patients. At the same time, confirming whether CDK4/6 inhibitors are equally applicable to Chinese breast cancer patients is not only an academic hotspot concerned by domestic clinicians, but also a practical need in actual diagnosis and treatment. This article reviews the classic clinical trials of drugs and the latest research progress.
9.Investigation and Analysis of Network Security of Health Industry in Shandong Province
Donghai XU ; Xiaohui QU ; Zhiguo LIU ; Yong LI ; Shiliang CHENG ; Guofeng BAO
Journal of Medical Informatics 2023;44(11):41-45
Purpose/Significance To investigate and analyze the current situation of health industry network security in Shandong province,to pinpoint the network security weaknesses,and to improve the decision-making capacity of risk management.Method/Process Based on the data collected by questionnaires,the gap analysis of network security is conducted from the two dimensions of the level and regional distribution of medical institutions.Result/Conclusion In view of the problems faced by the informatization construction of primary medical and health institutions at the management level and the technical protection level,the specific solutions to the network security governance of health industry are put forward.
10.Short-term efficacy of sublingual immunotherapy in patients with allergic rhinitis of all ages
Xuan TANG ; Lixin YANG ; Donghai LI
Chinese Journal of Primary Medicine and Pharmacy 2022;29(12):1859-1861
Objective:To investigate the short-term efficacy of sublingual immunotherapy in patients with allergic rhinitis of all ages.Methods:The data of 230 patients with allergic rhinitis of all ages who received sublingual immunotherapy in The Third People's Hospital of Bengbu from November 2020 to September 2021 were included in this study. Patient distribution characteristics were analyzed. Ninety-three patients were randomly selected and divided into child, adolescent, and adult groups according to different ages. Total nasal symptom scores measured before and 4 months after sublingual immunotherapy were compared among patients of different ages to evaluate the short-term efficacy of sublingual immunotherapy. The skin prick test was used to determine the allergic state of patients. Change in total nasal symptom score after treatment relative to that before treatment was used to evaluate the efficacy of sublingual immunotherapy.Results:The age range of patients receiving sublingual immunotherapy was large (3-71 years), but the average age was only 17.70 years. Ninety-three patients were followed up, including 50 children and 43 adolescents or adults. After 4 months of sublingual immunotherapy, total nasal symptom score in children and adolescents or adults were significantly decreased compared with those before treatment [(3.66 ± 1.69) points vs. (6.60 ± 1.96) points, (3.49 ± 1.72) points vs. (6.28 ± 2.28) points, both P < 0.001]. Before and after treatment, there was no significant difference in total nasal symptom score between children and adolescents or adults (both P > 0.05). Conclusion:Patients with allergic rhinitis who receive sublingual immunotherapy tend to be young. Short-term sublingual immunotherapy is effective for allergic rhinitis. There is no remarkable difference in the efficacy of sublingual immunotherapy between patients with allergic rhinitis of all ages.

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