ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

OBJECTIVE To systematically evaluate the correlation between dynamic changes in inflammatory markers during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in non-small cell lung cancer （NSCLC） patients and therapeutic efficacy， with the aim of providing evidence-based support for clinical prognosis assessment and treatment strategy adjustment. METHODS Databases including PubMed， Embase， Cochrane Library， CNKI， Wanfang Data， and CBM were searched from the inception to July 20， 2025. Following literature screening， data extraction and quality assessment， descriptive analysis was conducted on the outcomes of included studies. RESULTS A total of eight studies were included to analyze the correlation of 6 inflammatory markers before and after treatment with EGFR-TKIs with therapeutic efficacy. The risk of bias assessment identified six high-quality studies and two moderate-quality studies. Among these studies， seven studies demonstrated that lower levels of neutrophil-to-lymphocyte ratio （NLR）， derived neutrophil-to-lymphocyte ratio （dNLR）， platelet-to-lymphocyte ratio （PLR）， and monocyte-to-lymphocyte ratio （MLR）， higher lymphocyte-to-monocyte ratio （LMR） before treatment， as well as decreased NLR and MLR and increased LMR after treatment were associated with longer median progression-free survival. Five studies indicated that lower levels of NLR， dNLR， PLR， and interleukin-6 （IL-6）， higher LMR before treatment as well as decreased NLR and dNLR and increased LMR were associated with longer median overall survival. Three studies indicated that lower levels of IL-6 were associated with a higher objective response rate， while the association of these markers after treatment remained controversial； another study showed that an early decline in NLR， MLR， and PLR after treatment may be associated with objective response benefit. CONCLUSIONS Lower inflammatory levels during EGFR-TKIs therapy correlate with better therapeutic efficacy in NSCLC patients.

OBJECTIVE: To observe the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on learning-memory ability and hippocampal mammalian sterile 20-like kinase 1 (Mst1)/nuclear factor κB (NF-κB) p65 pathway related to inflammatory response in rats with vascular dementia (VD). METHODS: A total of 60 male Wistar rats of SPF grade were randomly divided into a sham operation group (12 rats) and a modeling group (48 rats). VD model was established by the method of modified bilateral common carotid artery permanent ligation in the modeling group. Thirty-six rats with successful modeling were randomly divided into a model group, a moxibustion group and a western medication group, with 12 rats in each group. Huayu Tongluo moxibustion was applied at "Dazhui" (GV14), "Baihui" (GV20) and "Shenting" (GV24) in the moxibustion group, 20 min each time, once a day, 7 day-intervention was as one course, and 1 day-interval was taken between two courses, for a total of 3 courses. In the western medication group, piracetam was given 0.72 mg/kg by intragastric administration, twice a day, the course of intervention was same as that of the moxibustion group. The learning-memory ability was detected by Morris water maze test; the morphology of hippocampal CA1 region was observed by HE staining; the mRNA expression of Mst1, M1 microglia markers CD86, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by real-time PCR; the levels of IL-6 and TNF-α in hippocampus were detected by ELISA; and the protein expression of Mst1 and NF-κB p65 in hippocampus was detected by Western blot in rats of each group. RESULTS: Compared with the sham operation group, the escape latency was prolonged in the model group (P<0.05); compared with the model group, the escape latency was shortened in the moxibustion group and the western medication group (P<0.05). The cells in the CA1 region of hippocampus were disordered, cell collapse and irregular nuclei could be observed in the model group; compared with the model group, the cell arrangement in the CA1 region of hippocampus was more regular, and the damage was improved in the moxibustion group and the western medication group. Compared with the sham operation group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were increased in the model group (P<0.05). Compared with the model group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). Compared with the sham operation group, the levels of IL-6 and TNF-α in hippocampus were increased in the model group (P<0.05). Compared with the model group, the levels of IL-6 and TNF-α in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). CONCLUSION Huayu Tongluo moxibustion can improve the learning-memory ability of VD rats, the mechanism may be related to regulating the activation of microglia through Mst1/NF-κB p65 pathway, reducing the release of pro-inflammatory factors i.e. IL-6 and TNF-α, so as to alleviating the damage of inflammatory factors in the hippocampus of VD rats.
Animals ; Male ; Rats ; Moxibustion ; Hippocampus/metabolism* ; Rats, Wistar ; Dementia, Vascular/genetics* ; Memory/drug effects* ; Humans ; Transcription Factor RelA/genetics* ; Learning ; Protein Serine-Threonine Kinases/genetics* ; Acupuncture Points ; Interleukin-6/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal

The paper summarizes Professor YANG Jun's experience in treatment of refractory facial paralysis with the refined mode of acupuncture and moxibustion, so as to provide new ideas and methods for the disease treated with acupuncture and moxibustion. Professor YANG Jun puts forward the refined mode of diagnosis and treatment of acupuncture and moxibustion for refractory facial paralysis. On the basis of syndrome/pattern differentiation of TCM, combined with meridian theory and modern anatomy, the symptom differentiation and meridian differentiation are performed accurately. By selecting local acupoints (e.g. Touwei [ST8], Sibai [ST2], Cuanzhu [BL2] and Yangbai [GB14]), distal acupoints (e.g. Zusanli [ST36], Hegu [LI4] and Jinsuo [GV8]), specific acupoints (e.g.Qianzheng [EX-HN16] and Touqiaoyin [GB11]) and the acupoints for regulating the mind (e.g. Dazhui [GV14] and Shuigou [GV26]), the prescription is composed. The different needling techniques are delivered at the acupoints (e.g. point-to-point needling with long needle, stuck needling by lifting and dragging, and balance needling on the healthy side). Besides, the facial rehabilitation is considered as the adjuvant treatment. This mode of treatment obtains the precise diagnosis and treatment to achieve the utmost therapeutic effects.
Humans ; Moxibustion ; Acupuncture Therapy/history* ; Facial Paralysis/therapy* ; Acupuncture Points ; Male ; Meridians ; Female ; History, 21st Century ; History, 20th Century

BACKGROUND:Much of the current research on M2 macrophage-derived exosomes focuses on their effects on wound healing and osteoblast proliferation and differentiation,while few studies have focused on their role in regulating microglia phenotype.OBJECTIVE:To discuss the role and molecular mechanisms of M2 macrophage-derived exosomes in the phenotypic regulation of microglia.MERHODS:(1)Bone marrow primary macrophages were extracted and then stimulated with 50 ng/mL interleukin 4 for 24 hours to promote macrophage M2-type polarization.Flow cytometry and cellular immunofluorescence were used to identify the M2-type macrophage marker CD206.(2)M2 macrophage-derived exosomes were extracted and identified.(3)Microglia BV2 were randomly divided into three groups:control group,lipopolysaccharide group,and treatment group.No treatment was done in the control group.500 ng/mL lipopolysaccharide was added to the intervention for 24 hours in the lipopolysaccharide group.500 ng/mL lipopolysaccharide and 25 μg/mL M2 macrophage-derived exosomes were added simultaneously to the treatment group for 24 hours.ELISA was performed to detect the secretion of tumor necrosis factor α and interleukin 10 in the culture supernatant.qRT-PCR was performed to detect the mRNA expression of inducible nitric oxide synthase,arginase 1,interleukin 1β,and interleukin 10 in the cells.Western blot assay was performed to detect the protein expression of inducible nitric oxide synthase,arginase 1,and nuclear factor-κB signaling pathway related protein expression.RESULTS AND CONCLUSION:(1)ELISA results showed that the secretion of tumor necrosis factor α was significantly increased in the lipopolysaccharide group compared with the control group.The secretion of tumor necrosis factor α was reduced and the secretion of interleukin 10 was increased in the treatment group compared with the lipopolysaccharide group.(2)The qRT-PCR results showed that compared with the control group,the mRNA expression of interleukin 1β and inducible nitric oxide synthase increased in the lipopolysaccharide group.Compared with the lipopolysaccharide group,the mRNA expression of interleukin 1β and inducible nitric oxide synthase decreased,and the mRNA expression of interleukin 10 and arginase 1 increased in the treatment group.(3)Western blot assay results showed that the expression of inducible nitric oxide synthase protein was increased in the lipopolysaccharide group compared with the control group.The expression of inducible nitric oxide synthase protein was decreased and the expression of arginase 1 protein was elevated in the treatment group compared with the lipopolysaccharide group.(4)Compared with the control group,the expression of p65 and p-IκB-α proteins in the nuclear factor-κB signaling pathway was reduced in the lipopolysaccharide group,whereas the expression of p65 and p-IκB-α proteins was elevated in the treatment group compared with the lipopolysaccharide group.The results showed that M2-type macrophage-derived exosomes could significantly inhibit lipopolysaccharide-induced inflammatory responses in microglia,enhance the expression of the anti-inflammatory factor interleukin 10,suppress the expression of the pro-inflammatory factors tumor necrosis factor α and interleukin 1β,and promote microglial cell phenotypes polarized from the M1-type to the M2-type.The mechanism may be related to the inhibition of nuclear factor-κB signaling pathway activation by M2-type macrophage-derived exosomes.

Objective:To investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective To achieve non-invasive and precise prediction of mean arterial pressure(MAP)based on a fully convolutional neural network(FCNN).Methods A high-precision blood pressure data acquisition system compliant with international metrological standards was used in conjunction with the'gold standard'auscultation method to collect blood pressure and pulse waveform data from patients.True MAP values were derived via Gaussian fitting of pulse waveform data,constructing a traceable dataset.The FCNN was applied to this dataset to develop a novel MAP prediction method.Additionally,the predictive accuracy of the FCNN was compared with linear regression and conventional empirical formulas.Results The mean squared errors(MSE)for MAP prediction using the FCNN,linear regression,and empirical formulas were 19.76,21.40,and 30.97,respectively.The coefficients of determination(R2)were 0.90,0.89,and 0.84,and the prediction accuracies were 0.90,0.89,and 0.85,respectively.Conclusions By using systolic blood pressure,diastolic blood pressure,age,and arm circumference as input parameters,the FCNN-based MAP prediction method significantly reduces the bias of empirical formulas.This approach not only improves the accuracy of hemodynamic boundary condition acquisition but also contributes to refining the metrological traceability system of non-invasive blood pressure measurement.

AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.