As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Objective:To assess the burden and development trends of tuberculosis (TB) in China from 1990 to 2021 to provide a reference for TB prevention strategies.Methods:Utilizing the 2021 Global Burden of Disease Study data, the study evaluates the burden of TB and latent TB infection (LTBI) in China using age-standardized incidence, prevalence, disability-adjusted life years (DALYs), and infection rates. The Joinpoint regression model was employed to analyze changing trends, and the autoregressive moving average model was integrated to forecast multidrug-resistant TB incidence and LTBI infection rates from 2022 to 2030.Results:In 2021, the age-standardized TB incidence in China was 36.28 per 100 000, the age-standardized prevalence was 30 557.45 per 100 000, the age-standardized DALY rate was 76.22 per 100 000, and the LTBI age-standardized infection rate was 30.48%. Compared to 1990, these figures dropped by 66.72%, 2.82%, 89.41%, and 2.47%, respectively. The age-standardized incidence, prevalence, DALY rate, and infection rate were elevated in individuals aged ≥70 years, and the TB burden was greater in males than in females. The age-standardized TB incidence declined between 1990 and 2021, while the proportion of multidrug-resistant TB patients among newly diagnosed cases, nationwide rose from 3.11% (36 367/1 167 807) in 1990 to 4.12% (25 431/617 725) in 2021. The LTBI age-standardized infection rate exhibited a fluctuating declining trend, averaging a decrease of 0.09%. Predictions for 2022-2030 indicate that China's multidrug-resistant TB incidence will decline slowly, and the LTBI infection rate will initially rise and then gradually fall, reaching 1.10/100 000 and 31.11%, respectively, by 2030.Conclusions:The TB burden in China declined from 1990 to 2021, but TB prevalence and LTBI infection rates remain high, especially among multidrug-resistant cases, males, and the elderly. Implementing systematic LTBI interventions, enhancing early detection/diagnosis in key populations such as the elderly, and promoting short-course treatments are recommended.

Objective To investigate the clinical effect of elastic fixation of Endobutton plate with loop in the treatment of lower tibiofibular combined injury.Methods A total of 326 patients with lower tibiofibular joint injury combined with ankle fracture underwent surgical treatment from June 2019 to June 2021 were randomly divided into experimental group(163 cases)and control group(163 cases)by using a random number table.The control group was fixed with traditional steel plate screw,and the experimental group was fixed with elastic steel plate with loop Endobutton.Hospitalization and operation related indexes were compared between the two groups.The American Association of Foot and Ankle Surgery Ankle Function Score(AOFAS)was performed on the two groups at 2 and 6 months after surgery,respectively,and the reseparation rate of the lower tibiofibular union was evaluated and compared between the two groups at 6 months after surgery.Results There were no significant differences in operation time,blood loss,incision length,getting out of bed time and hospital stay between experimental group and control group(P＞0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference between the two groups was statistically significant(P＜0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference was statistically significant between the two groups(P＜0.05).The AOFAS scores of control group were(74.5±9.2)and(81.3±4.3)at 2 months and 6 months,respectively,and the excellent and good rate was 76.0％.AOFAS of experimental group were(82.3±5.3)points and(91.2±3.8)points at 2 months and 6 months after surgery,respectively,and the excellent and good rate was 93.2％,the above indexes of experimental group were higher than those of control group,and the difference between the two groups was statistically significant(P＜0.05).Reexamination 6 months after surgery the reseparation rate of lower tibiofibular combination was 12.8％in the control group and 2.4％in the experimental group,and the risk of reseparation in the experimental group was lower than that in the control group,with statistical significance(P＜0.05).Conclusion Elastic fixation using Endobutton plate with loop could be used in the treatment of ankle fracture with distal tibiofibular syndesmosis injury,which has a better effect of traditional internal fixation with plate and screws.

Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

Objective:To investigate the effects of circular RNA fascin actin-bundling protein 1(circFSCN1)on the malignant biological behaviors of gastric cancer cells by regulating the microRNA-429(miR-429)/glycoprotein nonmetastatic melanoma protein B(GPNMB)axis and its mechanisms.Methods:The gastric cancer tissues and corresponding para-cancerous tissues of 54 patients who underwent surgical resection at the First Hospital of Hebei Medical University between September 2022 and September 2023 were collected.The expressions of circFSCN1,miR-429 and GPNMB mRNA in gastric cancer tissues were detected by qPCR.Gastric cancer MGC803 cells were routinely cultured and divided into the control group,the sh-NC group,the sh-circFSCN1 group,the sh-circFSCN1+anti-NC group,and the sh-circFSCN1+anti-miR-429 group.The expressions of circFSCN1,miR-429 and GPNMB mRNA in MGC803 cells of each group were detected by qPCR.The proliferation,migration,invasion and apoptosis of MGC803 cells in each group were detected by CCK-8 method,colony formation assay,Transwell assay and flow cytometry,respectively.Immunofluorescence was used to detect the expressions of GPNMB protein in cells of each group.WB assay was used to detect the expressions of PCNA,MMP-2,GPNMB and Cleaved Caspase-3 proteins in MGC803 cells of each group.Dual luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay were used to verify the binding regulatory relationship between circFSCN1 and miR-429,and between miR-429 and GPNMB.Results:circFSCN1 and GPNMB mRNA were both highly expressed in gastric cancer tissues(both P<0.05),while miR-429 was lowly expressed(P<0.05).Knockdown of circFSCN1 could promote the expression of miR-429 and inhibit the expression of GPNMB mRNA.Inhibition of miR-429 could promote the expression of GPNMB mRNA.Knockdown of circFSCN1 could significantly inhibit the proliferation,migration and invasion abilities of MGC803 cells and promote their apoptosis.Inhibition of miR-429 could partially reverse the effect of circFSCN1 knockdown.Knockdown of circFSCN1 could inhibit the expressions of PCNA,MMP-2 and GPNMB proteins in MGC803 cells and inhibit the expression of cleaved caspase-3 protein.There was a targeted binding and negative regulatory relationship between circFSCN1 and miR-429 and between miR-429 and GPNMB mRNA.Conclusion:Knocking down circFSCN1 inhibits the malignant biological behaviors of gastric cancer cells through the miR-429/GPNMB axis,indicating that circFSCN1 is a potential therapeutic target for gastric cancer.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.