ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR＜0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95％CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P＜0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Due to their unique physicochemical properties, nanomaterials can optimize drug delivery and reshape the tumor microenvironment. Manganese-based nanomaterials are primarily used in tumor immunotherapy for the following purpose, including targeted activating of the cyclic GMP-AMP synthase-stimulator of interferon gene pathway to enhance immunogenicity, utilizating of manganese′s redox properties to regulate the tumor microenvironment, and developing of manganese-based magnetic resonance imaging contrast agents to monitor immune responses in real time. In this review, synthesis methods of manganese-based nanomaterials such as thermal decomposition method, hydrothermal/solvothermal synthesis method, and chemical precipitation/mixing method as well as an in-depth analysis of their applications in tumor immunotherapy including immune regulation, regulation of tumor microenvironment and enhanced magnetic resonance imaging were reviewed.

Although patients with stage pT 2-3N 0M 0 thoracic esophageal squamous cell carcinoma are staged earlier, their postoperative local recurrence and distant metastasis rates are higher, resulting in a low five-year survival rate of such patients. The current neoadjuvant treatment for such patients is still in the research stage, and whether to give adjuvant radiotherapy and chemotherapy after surgery is still controversial. In addition, the prognostic factors of patients with pT 2-3N 0M 0 thoracic esophageal squamous cell carcinoma have not yet been clarified, and the causes of recurrence and metastasis are not yet clear. Therefore, it is of great significance to clarify treatment strategies and explore the impact of prognostic factors on improving the survival rate of such patients, which is expected to provide new directions for improving the prognosis and survival rate of patients with pT 2-3N 0M 0 thoracic esophageal squamous cell carcinoma.

Objective:To investigate the mechanism of Compound Mufurong Nasal Ointment in interfering with allergic rhinitis in young rats based on the Th1/Th2 cytokines and c-jun N-terminal kinase (JNK) signaling pathway.Methods:Totally 60 young SD male rats were divided into normal group, model group, experimental group, Western medicine group, and combination group according to random number table method, with 12 rats in each group. Except for the normal group, allergic rhinitis rat models were prepared by intraperitoneal injection of ovalbumin and nasal instillation of ovalbumin sensitization in all other groups of rats. After successful modeling, the normal group and the model group were given 0.9% sodium chloride injection 50 μl nasal drip, and the experimental group, the Western medicine group and the combination group were given compound Mufurong Nasal Ointment, fluticasone propionate nasal spray, compound Mufurong Nasal Ointment and fluticasone propionate nasal spray respectively. HE staining was used to observe the pathological morphology of nasal mucosal tissue; ELISA method was used to detect the levels of total IgE, interferon - γ (IFN - γ), IL-1 β, and IL-4 in the serum and nasal lavage fluid of rats in each group; Western blot was used to detect the expressions of JNK and p-JNK proteins in nasal tissues of rats in each group; Immunohistochemistry was used to detect the expressions of p-JNK and p-c-Jun proteins in nasal mucosal tissue.Results:Compared with model group, the levels of IgE, IL-1β and IL-4 in serum and nasal lavage solution of experimental group, western medicine group and combination group decreased ( P<0.05), IFN-γ level increased ( P<0.05); the expressions of JNK and p-JNK protein decreased ( P<0.05), and the expressions of p-JNK and p-c-Jun decreased ( P<0.05). Conclusion:Compound Mufurong Nasal Ointment may regulate Th1/Th2 cytokines through the JNK signaling pathway, inhibit Th2 over-expression, thereby reducing IgE, IL-1 β, IL-4 levels in serum and nasal lavage fluid, up-regulating IFN - γ levels, and intervening in the occurrence of allergic rhinitis.