Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

OBJECTIVE To investigate the effects of peiminine B （PEI） on Streptococcus pneumoniae （SP）-induced alveolar epithelial cell injury by regulating the Ras-related C3 botulinum toxin substrate 1 in nucleus accumbens （Rac1）/protein kinase B （Akt）/nuclear factor κB （NF-κB） signaling pathway. METHODS Human alveolar epithelial cells （HPAEpiC） were taken and randomly divided into the Control group， SP group （1×108 cfu/mL SP bacterial solution）， low-， medium-， and high-concentration PEI groups （1×108 cfu/mL SP bacterial solution+0.05， 0.10， 0.20 mmol/L PEI）， and high-concentration PEI+Akt activator group （P-H+SC79 group， 1×108 cfu/mL SP bacterial solution+0.20 mmol/L PEI+10 μmol/L SC79）. Except for the Control group， the other groups of cells were treated with SP bacterial solution and/or corresponding drug solution. After 24 h of treatment， the levels of inflammatory factors （interleukin-6， -18， -1β） in the supernatant solution， the contents of oxidative stress indexes [lactate dehydrogenase （LDH）， reactive oxygen species （ROS） and superoxide dismutase （SOD）]， apoptosis rate， as well as the expressions of proliferation/apoptosis-related proteins [cyclin-dependent kinase 1 （CDK1）， B cell lymphoma-2 related X protein （Bax）] and pathway-related proteins （Rac1， Akt， phosphorylated Akt， NF-κB and phosphorylated NF-κB） were detected in each group. RESULTS Compared with the Control group， the levels of inflammatory factors in supernatant solution， LDH and ROS contents， apoptosis rate， the protein expressions of Bax and Rac1 and the phosphorylation levels of Akt and NF-κB in the SP group were significantly increased or up-regulated， while SOD content and the protein expression of CDK1 were significantly decreased or down-regulated （P＜0.05）. Compared with the SP group， the above indexes in PEI groups were significantly improved in a concentration-dependent manner （P＜0.05）. SC79 could significantly reverse the improvement effect of the high concentration of PEI （P＜0.05）. CONCLUSIONS PEI can alleviate SP-induced inflammation and oxidative stress damage of alveolar epithelial cells and inhibit apoptosis， which may be achieved by inhibiting Rac1/Akt/NF-κB signaling pathway.

To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

ObjectiveTo develop a classification model based on complete blood count （CBC） parameters combined with clinical factors to predict severe respiratory infections caused by Human adenovirus （HAdV） in pediatric patients. MethodsFrom September 2023 to September 2024， the CBC parameters and related clinical data from pediatric patients diagnosed with HAdV infection were collected. Principal component analysis and random forest models were used to identify potential predictors of severe cases. ResultsA total of 668 pediatric patients were included， with 564 cases assigned to the training cohort and 104 cases to the validation cohort. Severe cases were defined as pneumonia and/or fever lasting ≥5 days （pneumonia or prolonged fever， PorPF）. Principal component analysis and feature importance analysis （Mean Decrease Gini value） identified the monocytosis ratio （PMono）， red blood cell count （RBC）， and platelet count （PLT） as the most critical CBC parameters. Logistic regression analysis revealed that oxygen therapy （OR = 4.367， 95% CI： 1.568–12.161） and increased work of breathing （OR = 3.904， 95% CI： 2.146–7.101） were relative risk factors for PorPF. Meanwhile， higher PMono （OR = 0.696， 95% CI： 0.640–0.757）， RBC （OR = 0.201， 95% CI： 0.124–0.325）， and PLT （OR = 0.990， 95% CI： 0.987–0.994） were protective factors. When PMono was used as a predictive marker for PorPF， the area under the receiver operating characteristic curve （AUC） was 0.648 and 0.705， respectively. A random forest model incorporating four risk factors ［PMono， RBC， PLT， and hematocrit （HCT）］ was constructed to classify PorPF and general cases， achieving AUCs of 0.688 and 0.768， respectively. ConclusionsPMono， RBC， and PLT may serve as characteristic CBC indicators for predicting pneumonia or prolonged fever in children with HAdV infection. A risk factor model built using PMono， RBC， PLT， and HCT offers a relatively simple and accurate approach to predicting severe cases in pediatric HAdV infections.

Objective To explore the evaluation value of serum follistatin like protein 1(FSTL1)and glu-cose regulatory protein 78(GRP78)on disease severity and readmission in elderly patients with chronic ob-structive pulmonary disease(COPD).Methods A total of 100 elderly COPD patients(COPD group)treated in this hospital from March 2020 to May 2023 were selected as COPD group,and were divided into grade Ⅰ(35 cases),grade Ⅱ(46 cases)and grade Ⅲ(19 cases)according to the severity of the disease.Another 100 elderly volunteers who underwent physical examination during the same period were selected as the control group.Serum FSTL1 and GRP78 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman and Pearson correlation were used to analyze the correlation between serum FSTL1 and GRP78 lev-els and general data.The evaluation value of serum FSTL1 and GRP78 levels in COPD patients on disease se-verity and readmission was analyzed by receiver operating characteristics(ROC)curve.Results Compared with the control group,serum levels of FSTL1 and GRP78 in COPD group were significantly increased(P＜0.05).Serum levels of FSTL1 and GRP78 in COPD patients increased with the severity of the disease(P＜0.05).Compared with non-readmission group,the serum levels of FSTL1 and GRP78 in readmission group were significantly increased(P＜0.05).Spearman correlation analysis showed that serum FSTL1 and GRP78 levels were positively correlated with smoking history,hypertension history and disease severity(P＜0.05).Pearson correlation analysis showed that serum FSTL1 and GRP78 levels were negatively correlated with arte-rial oxygen pressure(PaO2),the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC),and the percentage of forced expiratory volume in the first second to expected value(FEV1％pred),with significance(P＜0.05),while it was positively correlated with the partial pressure of carbon diox-ide(PaCO2),with significance(P＜0.05).ROC curve analysis showed that serum FSTL1,GRP78 and their combined assessment of disease severity and readmitted area under the curve(AUC)were higher in COPD pa-tients,and the combination was significantly better than the single assessment(P＜0.05).Conclusion Serum levels of FSTL1 and GRP78 are significantly increased in COPD patients,which are correlated with the severi-ty of the disease and have a high value in evaluating the severity of the disease and readmission.

Objective To investigate the predictive value of serum circular RNA(circRNA)CDYL and circRNA ACAP2 expression levels for major adverse cardiovascular events(MACE)in pa-tients with acute myocardial infarction(AMI).Methods A total of 98 AMI patients were enrolled into the observation group,and divided into MACE group(n=45)and no-MACE group(n=53)based on whether they experienced MACE.Another 98 healthy individuals who underwent physical ex-amination during the same period were selected as the control group.The expression levels of serum cir-cRNA CDYL and circRNA ACAP2 were compared among groups.Multivariate logistic regression analysis was used to identify factors influencing the occurrence of MACE in AMI patients.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of serum circRNA CDYL and circRNA ACAP2 levels for MACE in AMI patients.Results The serum circRNA CDYL level in the observation group was significantly lower than that in the control group,while the circRNA ACAP2 level was significantly higher(P＜0.05).The circRNA CDYL level in the MACE group was significantly lower,and the circRNA ACAP2 level was significantly higher than that in the no-MACE group(P＜0.05).Heart rate and circRNA ACAP2 were identified as independent risk factors for MACE in AMI patients,whereas circRNA CDYL served as independent protective factor(P＜0.05).The area under the ROC curve(AUC)for predicting MACE in AMI patients using se-rum circRNA CDYL,circRNA ACAP2 and their combination were 0.814,0.821 and 0.921,re-spectively.The sensitivity and specificity of combined prediction using serum circRNA CDYL and circRNA ACAP2 were 91.11％and 79.25％,respectively.The combined prediction efficacy of serum circRNA CDYL and circRNA ACAP2 was superior to their individual prediction(Zcombined-circRNA CDYL=1.975,Zcombined-circRNAACAP2=2.064,P=0.048,0.039).Conclusion Serum circRNA CDYL lev-el is down-regulated and circRNA ACAP2 level is up-regulated in AMI patients,and circRNA ACAP2 is an independent risk factor for MACE,while circRNA CDYL is a independent protective factor.The combined value of circRNA CDYL and circRNA ACAP2 in predicting the occurrence of MACE is higher.

Objective To investigate the cell membrane-penetrating capacity of human cell-penetrating peptide hPP10 carrying human antioxidant protein Cu-Zn superoxide dismutase(Cu,Zn-SOD)and assess the antioxidant and anti-inflammatory activity of these fusion proteins.Methods The fusion protein hPP10-Cu,Zn-SOD was obtained by genetic engineering and identified by Western blotting.The membrane-penetrating ability of the fusion protein was evaluated by immunofluorescence assay,fluorescence colocalization assay and Western blotting,its SOD enzyme activity was detected using a commercial kit,and its effect on cell viability was assessed with MTT assay.In a HEK293 cell model of H2O2-induced oxidative stress,the effect of hPP10-Cu,Zn-SOD on cell apoptosis was analyzed with flow cytometry and RT-qPCR,and its antioxidant effect was assessed using reactive oxygen species(ROS)assay;its anti-inflammatory effect was evaluated in mouse model of TPA-induced ear inflammation by detecting expression of the inflammatory factors using RT-qPCR,Western blotting and immunohistochemistry.Results The fusion protein hPP10-Cu,Zn-SOD was successfully obtained.Immunofluorescence assay confirmed obvious membrane penetration of this fusion protein in HEK293 cells,localized both in the cell membrane and the cell nuclei after cell entry.hPP10-Cu,Zn-SOD at the concentration of 5 μmol/L exhibited strong antioxidant activity with minimal impact on cell viability at the concentration up to 10 μmol/L.The fusion protein obviously inhibited apoptosis and decreased intracellular ROS level in the oxidative stress cell model and significantly reduced mRNA and protein expression of the inflammatory factors in the mouse model of ear inflammation.Conclusion The fusion protein hPP10-Cu,Zn-SOD capable of penetrating the cell membrane possesses strong antioxidant and anti-inflammatory activities with only minimal cytotoxicity,demonstrating the value of hPP10 as an efficient drug delivery vector and the potential of hPP10-Cu,Zn-SOD in the development of skincare products

Recent studies have identified that metabolic reprogramming in lung adenocarcinoma cells,particularly lactate metabolism disorders,plays a crucial role in tumor development and immune therapy response.The accumulation of lactic acid not only provides energy support for the proliferation of tumor cells but also affects the function of immune cells by changing the tumor microenvironment,thereby promoting immune escape.Immunotherapy,especially the application of immune checkpoint inhibitors,has become an important strategy for treating lung adenocarcinoma.However,lactate metabolism disorders might affect the efficacy of immunotherapy,leading to resistance in some patients.Therefore,a thorough understanding of the mechanisms of lactic acid metabolism in lung adenocarcinoma and its impact on the response to immu-notherapy is essential for developing new therapeutic strategies and improving the efficacy of immunoth-erapy.This review summarizes the role of lactate metabolism disorders in the development and immun-otherapy of lung adenocarcinoma,discusses the potential role of lactic acid metabolism-related genes and pathways in lung adenocarcinoma,and explores the progress in therapeutic strategies targeting lactic acid metabolism regulation.This work aims to provide new insights for the treatment of lung adenocarcinoma.