1.Structure and Function of The α9 Nicotinic Acetylcholine Receptor
Yi-Ning ZHENG ; Xu-Dong WANG ; San-Ling LIU
Progress in Biochemistry and Biophysics 2026;53(8):2220-2234
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels (pLGICs) that mediate rapid cholinergic synaptic transmission throughout the central and peripheral nervous systems. These receptors are integral to neuromuscular junction signaling, autonomic regulation, cognitive learning, reward-related behavior, and neuroplasticity. The nAChR family exhibits remarkable functional diversity through combinatorial assembly of seventeen identified subunits (α1-α10, β1-β4, γ, δ, and ε). Among these, the α9 subunit occupies a distinctive phylogenetic position, exhibiting greater sequence divergence from other neuronal α subunits and possessing unique biochemical properties that distinguish it from all other family members. α9 can form homopentamers and also co-assemble with the α10 subunit to form functional heteropentamers, primarily in (α9)2(α10)3 and (α9)3(α10)2 stoichiometries. This dual assembly strategy generates functional heterogeneity, as distinct subunit compositions confer differential ion permeation, ligand sensitivity, and desensitization kinetics. The structural determinants governing this stoichiometric variability remain incompletely resolved, representing a critical gap in our mechanistic understanding. Unlike most other nAChR subtypes, traditional agonists of nAChRs (such as nicotine) elicit virtually no agonistic effect on α9* nAChRs (α9-containing receptors, including α9 homopentamers and α9α10 heteropentamers). This pharmacological divergence reflects structural differences within the orthosteric site, particularly in regions at complementary subunit interfaces. As cation-selective channels, α9* nAChRs exhibit high permeability to Ca2+. In cochlear outer hair cells, α9α10 nAChRs mediate cholinergic efferent modulation by the medial olivocochlear (MOC) bundle. Acetylcholine-evoked Ca2+ influx activates functionally coupled SK2 potassium channels, generating net hyperpolarization that dampens electromechanical amplification through a tightly constrained signaling microdomain. This Ca2+-dependent excitatory-to-inhibitory conversion exemplifies sophisticated sensory gain control, and its disruption contributes to noise-induced hearing loss, age-related hearing loss, and tinnitus. Beyond canonical ionotropic signaling, α9* nAChR engages metabotropic transduction pathways. In macrophages, receptor activation modulates cytokine production and inflammatory responses. In keratinocytes, it regulates wound healing by modulating cell migration and differentiation. In dorsal root ganglion sensory neurons, α9* signaling contributes to nociceptive processing and inflammatory hyperalgesia. This functional pleiotropy, spanning both ionotropic signaling and metabotropic transduction, positions α9* nAChR as an exemplary model for investigating signal polymorphism within the pLGIC superfamily. Pathophysiologically, α9* nAChR dysfunction is implicated across multiple organ systems. In the auditory system, disruption of α9α10 nAChR-mediated MOC efferent feedback impairs cochlear gain control, predisposing to noise-induced synaptopathy and age-related hearing loss. In immune cells, dysfunctional α9* nAChR signaling disrupts cholinergic anti-inflammatory pathway activity, exacerbating pro-inflammatory responses. In the peripheral sensory system, aberrant α9* nAChR signaling has been implicated in neuropathic and inflammatory pain states. In skin, impaired receptor function compromises keratinocyte migration and re-epithelialization through disrupted signaling pathways, leading to chronic wound healing defects and inflammation. These pathophysiological associations have catalyzed pharmacological interest, yielding promising chemical entities including α‑conotoxins, small-molecule antagonists/agonists, and allosteric modulators.α-Conotoxin peptides, in particular, demonstrate remarkable subunit selectivity and potent antinociceptive effects in preclinical pain models. However, therapeutic translation faces substantial challenges: the broad tissue distribution of α9* nAChR risks on-target adverse effects in non-target organs; pronounced species differences between rodent and human receptors complicate preclinical validation; and the complexity of ionotropic-metabotropic signaling crosstalk demands pharmacological strategies that extend beyond conventional orthosteric agonism or antagonism. Looking forward, integrating cryo-electron microscopy of full-length receptors in distinct conformational states with single-channel electrophysiology and systems-level circuit analysis promises to illuminate the molecular mechanisms governing α9* nAChR function and regulation. The development of signal pathway-biased ligands and tissue-selective delivery strategies may ultimately harness the therapeutic potential of this receptor while mitigating safety liabilities. As a paradigm for understanding pLGIC signaling diversification, α9* nAChR research will continue to inform broader questions regarding ion channel evolution, allosteric regulation, and pathophysiological mechanisms of chronic pain and autoimmune inflammatory diseases.
2.Effect of adjusting the whole blood donation interval from 6 months to 3 months on blood donation adverse reactions and individual donation behavior: a multicenter, retrospective cohort study
Yuwei HU ; Ling LI ; Changping LI ; Yihang CHEN ; Kaokao ZHU ; Lin WANG ; Litao WU ; Liqin HUANG ; Chenying WANG ; Liu HE ; Li NING ; Zhong LIU
Chinese Journal of Blood Transfusion 2026;39(9):1179-1188
Objective: Some regions in China have lowered the minimum interval for whole blood donation to 3 months through local regulations: Hainan, effective from March 1, 2012, allows men to donate at intervals of≥3 months and women at intervals of≥4 months; Shenzhen, effective from November 1, 1995, allows whole blood donation at intervals of≥3 months. The aim of this study was to evaluate the impact of shortening the whole blood donation interval on blood donation adverse reactions and donation behavior, thereby providing scientific evidence for policy evaluation and revision of relevant regulations. Methods: This was a multicenter, retrospective cohort study based on blood donation registry data from Shenzhen and Hainan. Data were obtained from the blood information management systems of Hainan Province (1991-2025) and Shenzhen City (2018-2024). Eligible participants were donors aged 18-65 years who had donated whole blood at least twice and met health eligibility criteria. The exposure was defined as a shorter donation interval (whole-blood interval≥3 months and<6 months) and was treated as a time-varying variable. The primary outcome was blood donation adverse reactions. Negative binomial regression with person-years as an offset was used to estimate incidence rate ratios for adverse reactions. Marginal standardization was used to estimate the adjusted incidence rate difference, and donor-level bootstrap resampling was used to estimate the 95% confidence interval of the adjusted incidence rate difference. Non-inferiority was assessed by comparing the upper limit of the 95% confidence interval with the prespecified non-inferiority margin of Δ=0.00 070 per person-year. In addition, Andersen-Gill models were used to analyze adverse reaction-free probability for recurrent events. Secondary outcomes were donation behavior, including annual repeat donation rate, annual donation frequency, mean donation interval, and annual whole-blood donation volume. These were analyzed using logistic regression, negative binomial regression, and linear regression models, respectively, with adjustment for age, sex, region, and donation site. This study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (Approval No.2025011) and registered in the Chinese Clinical Trial Registry (ChiCTR2500114968). Results: A total of 375 075 repeat whole-blood donors were included, contributing 1 292 748 whole-blood donations. Among them, 119 993 had ever donated at a shorter interval and 255 082 had never done so. Over 1 281 842 person-years of follow-up in the dynamic cohort, 2 100 blood donation adverse reactions were recorded. The incidence rates of adverse reactions were 1.76 and 1.58 per 1 000 person-years in the ever-short interval and never-short interval groups, respectively. After adjustment for age, sex, province, and donation site, the ever-short interval group had a slightly higher adverse reaction rate than the never-short interval group (IRR=1.28, 95%CI: 1.15-1.41, P<0.001). Marginal standardization showed that the adjusted incidence rates were 1.73 and 2.21 per 1 000 person-years in the never-short interval and ever-short interval groups, respectively. The adjusted incidence rate difference was 0.000 48 per person-year, with a bootstrap 95%CI of 0.000 26-0.000 69 per person-year; the upper limit of the 95%CI was below the prespecified non-inferiority margin. Andersen-Gill recurrent-event analysis showed that the ever-short interval group had a higher probability of remaining adverse reaction-free. Analysis of donation behavior showed that among donors followed for at least 365 days, the ever-short interval group had a higher annual repeat donation rate than the never-short interval group (74.2% vs 18.3%; adjusted OR=12.5, 95%CI: 12.3-12.7, P<0.001). They also had a higher annual whole-blood donation rate (adjusted RR=1.98, 95%CI: 1.97-1.98, P<0.001), a shorter mean whole-blood donation interval (β=-239 days, 95%CI: -242 to -237 days, P<0.001), and a higher annual whole-blood donation volume (adjusted RR=2.14, 95%CI: 2.13-2.15, P<0.001). Conclusion: Based on real-world data from repeat whole-blood donors in Shenzhen and Hainan, lowering the minimum whole blood donation interval to 3 months did not show an absolute increase in blood donation adverse reactions exceeding the prespecified margin within the scope of this outcome. Shorter whole-blood donation interval behavior was also associated with greater repeat-donation activity, higher annual donation frequency, and higher annual whole-blood donation volume. Given the observational nature of this study and the lack of long-term donor health indicators such as iron status and longitudinal hemoglobin changes, the long-term safety of setting the minimum whole blood donation interval at 3 months requires further evaluation.
3.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
4.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
5.Predictive factors and nomogram model construction for plastic bronchitis in children with Mycoplasma pneumoniae pneumonia.
Wen-Hui WANG ; Fang-Fang YANG ; Ling-Jian MENG ; Ning MAO ; Yi WU
Chinese Journal of Contemporary Pediatrics 2025;27(10):1212-1219
OBJECTIVES:
To investigate the predictive factors for plastic bronchitis (PB) in children with Mycoplasma pneumoniae pneumonia (MPP) and to establish a nomogram prediction model for PB occurrence.
METHODS:
A retrospective analysis was conducted on children with MPP hospitalized at The Affiliated Hospital of Xuzhou Medical University from January 2023 to June 2024. The patients were randomly divided into a training set (n=562) and a validation set (n=240) at a ratio of 7:3 using simple random sampling. In the training set, patients were categorized into a PB group (n=70) and a non-PB group (n=492) based on the occurrence of PB. Spearman correlation analysis was performed to exclude collinearity among variables, followed by univariate analysis and LASSO regression to identify predictive factors. A nomogram prediction model for PB in children with MPP was constructed. The discriminative ability of the model was assessed using receiver operating characteristic (ROC) curve analysis, model calibration was evaluated with calibration curves, and clinical utility was appraised through decision curve analysis.
RESULTS:
Compared with the non-PB group, the PB group exhibited significantly longer disease duration prior to bronchoscopy, prolonged fever duration, higher fever peaks, higher proportions of patients with a family history of allergy and personal allergy history, and a higher proportion of patients with pleural effusion, as well as significantly elevated levels of white blood cell count, neutrophil percentage, C-reactive protein, procalcitonin, fibrinogen, D-dimer, aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, immunoglobulin A, and interleukin-6, along with a significantly lower lymphocyte percentage (all P<0.05). LASSO regression analysis identified pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase as major predictive factors for PB occurrence in children with MPP. The nomogram model based on these factors demonstrated good discriminative ability (area under the ROC curve: 0.852 in the training set and 0.830 in the validation set), with satisfactory calibration and clinical benefit.
CONCLUSIONS
The nomogram prediction model based on pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase provides effective predictive performance for the occurrence of PB in children with MPP.
Humans
;
Pneumonia, Mycoplasma/complications*
;
Nomograms
;
Male
;
Female
;
Child
;
Child, Preschool
;
Retrospective Studies
;
Bronchitis/etiology*
;
Infant
;
ROC Curve
;
Adolescent
6.Clinical Applications of Circulating Tumor DNA in Response Evaluation and Relapse Monitoring of Primary Mediastinal Large B-Cell Lymphoma.
Lu PAN ; Xin-Miao JIANG ; Yan TENG ; Ning WANG ; Ling HUANG ; Han-Guo GUO ; Si-Chu LIU ; Xiao-Juan WEI ; Fei-Li CHEN ; Zhan-Li LIANG ; Wen-Yu LI
Journal of Experimental Hematology 2025;33(2):407-415
OBJECTIVE:
To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL).
METHODS:
The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS).
RESULTS:
Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy.
CONCLUSION
CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans
;
Circulating Tumor DNA/blood*
;
Female
;
Mediastinal Neoplasms
;
Male
;
Retrospective Studies
;
High-Throughput Nucleotide Sequencing
;
Prognosis
;
Lymphoma, Large B-Cell, Diffuse/genetics*
;
Middle Aged
;
Adult
;
Aged
;
Neoplasm Recurrence, Local
;
Mutation
7.Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.
Xiao-Qian SUN ; Xuan LI ; Yan-Qin LI ; Xiang-Yu LU ; Xiang-Ning LIU ; Ling-Wen CUI ; Gang WANG ; Man ZHANG ; Chun LI ; Wei WANG
Chinese journal of integrative medicine 2025;31(3):215-227
OBJECTIVE:
To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation.
METHODS:
In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.
RESULTS:
QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism.
CONCLUSIONS
QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals
;
Myocardial Infarction/physiopathology*
;
Male
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Rats, Sprague-Dawley
;
Glucose/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Energy Metabolism/drug effects*
;
Rats
;
Fatty Acids/metabolism*
;
Myocardium/pathology*
8.Andrographolide sulfonate alleviates rheumatoid arthritis by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Chunhong JIANG ; Xi ZENG ; Jia WANG ; Xiaoqian WU ; Lijuan SONG ; Ling YANG ; Ze LI ; Ning XIE ; Xiaomei YUAN ; Zhifeng WEI ; Yi GUAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):480-491
Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4+ IL-17A+ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals
;
Th17 Cells/immunology*
;
Diterpenes/pharmacology*
;
Arthritis, Rheumatoid/metabolism*
;
Proto-Oncogene Proteins c-akt/immunology*
;
Glycolysis/drug effects*
;
Cell Differentiation/drug effects*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Rats
;
Male
;
Rats, Sprague-Dawley
;
Humans
;
Andrographis paniculata/chemistry*
;
Arthritis, Experimental/drug therapy*
;
Interleukin-17/immunology*
;
Signal Transduction/drug effects*
9.Application of PLIBEL and REBA for identifying and assessing the risk of work-related musculoskeletal disorders among medical staff
Tongsu ZHANG ; Ruijie LING ; Jingzhi SUN ; Zhongxu WANG ; Ning JIA ; Chuansha WU ; Yan YANG ; Fei LIU ; Hong YIN
China Occupational Medicine 2025;52(6):618-623
Objective To identify potential ergonomic risk factors of works and quickly assess their risks of developing work-related musculoskeletal disorders (WMSDs) in the medical staff. Methods A total of 188 medical staff were selected as the research objects using a two-stage random sampling method. The method for the identification of musculoskeletal stress factors (PLIBEL) was used to analyze the adverse ergonomic factors in the work process, and the rapid entire body assessment (REBA) was used to quickly assess the whole-body posture load. Results The PLIBEL assessment results showed that various adverse ergonomic factors affected different parts of the body during the work process of medical staff. Specifically, 18 adverse ergonomic factors were identified in the neck, shoulders, and upper back, while 10 adverse ergonomic factors were identified in the elbow, forearm, hand, and lower back. Rehabilitation therapists and nurses engaged in patient handling in general wards and medication preparation and blood collection were exposed to ≥35 adverse ergonomic factors. The REBA assessment showed that the REBA score was 3-12 points for medical staff during their work process. Rehabilitation therapists were classified as having an extremely high ergonomic risk. High-risk occupations included ward housekeeping nurses, surgery assistant nurses, operating-room instrument nurses, and surgeons. Medium-risk occupations included general ward nurses (medication preparation and blood collection, venipuncture/infusion, and patient handling), intensive care unit (ICU) nurses, internal medicine residents, and dentists. Low-risk occupations included administrative front-desk nurses, outpatient internal medicine physicians, and technicians/physicians in ultrasonography, laboratory medicine, physical examination, and occupational health departments. Conclusion Adverse ergonomic factors of medical staff predominantly affect the neck, shoulders, upper back, elbows, forearms, hands, and the lower back during the work process. Rehabilitation therapists, ward housekeeping nurses, ICU nurses, operating-room instrument nurses, and surgeons are high-risk groups for WMSDs. Attention should be paid to the management and control of adverse ergonomic factors for medical staff to prevent the occurrence of WMSDs.
10.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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