Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Objective:To explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis of pathogens in primary infectious diseases of the spine (IDS) and to reveal its pathogen spectrum.Methods:This is a retrospective multi-center case series study. Clinical data of 380 patients with primary IDS who were treated at four medical centers in China from December 2019 to April 2024 were retrospectively analyzed. Among them, 82 cases were from the Department of Spine Surgery at the Affiliated Hospital of Qingdao University, 129 cases were from the Orthopedics Section Ⅱ (Bone Infection), Public Health Clinical Center Affiliated to Shandong University, 112 cases were from the Department of Spine Surgery, Fuzhou Second General Hospital, and 57 cases were from the Department of Orthopedic Surgery, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. There were 238 males and 242 females, with an age of (61.4±13.1) years (range: 10 to 91 years). Specimens from the site of spinal infection were obtained for pathogen culture, pathological examination, and mNGS detection preoperatively or intraoperatively in all patients. The number, types, and positive rates of pathogens detected by the two methods were analyzed and compared using the Chi-square test.Results:Among the 380 patients, 320 had confirmed pathogenic bacteria, with the highest proportion being pyogenic bacterial infections, accounting for 76.9% (246/320). The most common pathogen was Staphylococcus aureus, accounting for 22.8% (73/320). Brucella accounted for 13.8% (44/320); Mycobacterium tuberculosis accounted for 6.3% (20/320). Fungal infections accounted for 3.4% (11/320), mainly Aspergillus and Candida. In addition, Mycoplasma was detected in 3 cases (0.9%) and Benacox body in 4 cases (1.2%). The pathogen spectrum constructed by mNGS covered 46 types of pathogens, higher than the 22 types detected by traditional methods. The positive rate of mNGS was 80.8% (308/381), significantly higher than the 27.9% (106/381) of traditional methods ( χ2=182.53, P<0.01). Conclusions:mNGS improves the positive rate of pathogen diagnosis in IDS, detecting a broader spectrum of pathogens, and serves as a valuable complement to traditional diagnostic methods. Combining both methods in the diagnosis of IDS can maximize detection rates, providing robust evidence for precise anti-infective treatment.

Objective:To explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis of pathogens in primary infectious diseases of the spine (IDS) and to reveal its pathogen spectrum.Methods:This is a retrospective multi-center case series study. Clinical data of 380 patients with primary IDS who were treated at four medical centers in China from December 2019 to April 2024 were retrospectively analyzed. Among them, 82 cases were from the Department of Spine Surgery at the Affiliated Hospital of Qingdao University, 129 cases were from the Orthopedics Section Ⅱ (Bone Infection), Public Health Clinical Center Affiliated to Shandong University, 112 cases were from the Department of Spine Surgery, Fuzhou Second General Hospital, and 57 cases were from the Department of Orthopedic Surgery, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. There were 238 males and 242 females, with an age of (61.4±13.1) years (range: 10 to 91 years). Specimens from the site of spinal infection were obtained for pathogen culture, pathological examination, and mNGS detection preoperatively or intraoperatively in all patients. The number, types, and positive rates of pathogens detected by the two methods were analyzed and compared using the Chi-square test.Results:Among the 380 patients, 320 had confirmed pathogenic bacteria, with the highest proportion being pyogenic bacterial infections, accounting for 76.9% (246/320). The most common pathogen was Staphylococcus aureus, accounting for 22.8% (73/320). Brucella accounted for 13.8% (44/320); Mycobacterium tuberculosis accounted for 6.3% (20/320). Fungal infections accounted for 3.4% (11/320), mainly Aspergillus and Candida. In addition, Mycoplasma was detected in 3 cases (0.9%) and Benacox body in 4 cases (1.2%). The pathogen spectrum constructed by mNGS covered 46 types of pathogens, higher than the 22 types detected by traditional methods. The positive rate of mNGS was 80.8% (308/381), significantly higher than the 27.9% (106/381) of traditional methods ( χ2=182.53, P<0.01). Conclusions:mNGS improves the positive rate of pathogen diagnosis in IDS, detecting a broader spectrum of pathogens, and serves as a valuable complement to traditional diagnostic methods. Combining both methods in the diagnosis of IDS can maximize detection rates, providing robust evidence for precise anti-infective treatment.

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system X_c^-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Paridis Rhizoma possesses the functions of clearing heat and detoxifying， alleviating swelling and relieving pain， cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer， lung cancer， gastric cancer， and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation， migration， and invasion of tumor cells， regulating cell cycle， inducing apoptotic and non-apoptotic death pathways， and regulating metabolism and tumor microenvironment. Furthermore， total saponins in Paridis Rhizoma showed anti-inflammatory， antioxidant， antimicrobial， hemostatic， and uterus-contracting activities. At the same time， they may induce apoptosis of normal cells， inflammation and oxidative stress， and metabolic disorders. In recent years， the reports of liver injury， reproductive injury， gastrointestinal injury， hemolysis， and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate， while oral administration may have hepatoenteric circulation. Meanwhile， due to the low solubility and activation of P-glycoprotein （P-gp） molecular pump， the prototype absorption， intestinal permeability， and recovery rate of total saponins in Paridis Rhizoma are poor， which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect， pharmacokinetics， and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure （CNKI）， VIP， and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords， hoping to provide references for the research， development， and clinical application of such components.

Objective To analyze the application of intelligent speech follow-up system in sec-ondary prevention of ischemic stroke(IS).Methods A total of 842 IS patients who received intra-venous thrombolysis were randomly divided into intelligent group and artificial group.In the artificial group,corresponding intelligent follow-up templates were developed for the main risk factors affecting the occurrence of IS.The intelligent follow-up system determined the follow-up time and period ac-cording to the reserved information of patients when they were discharged,automatically called out the patients'home conditions for follow-up,and converted the response contents into text mode for out-put.The artificial group was followed up by professionally trained nursing staff,and the follow-up con-tent was the same as that of the intelligent group.Call out,hypertension,diabetes,medication,exer-cise,average call time and satisfaction of follow-up in the two groups were collected.Results The tel-ephone connection rates showed no statistical significances between two groups(P＞0.05).During the follow-up calls,the correct recognition rate of follow-up contents in the intelligent group was low-er,and therateof unwillingness to cooperate and call interruption rate were higher than those in the control group(P＜0.05).There were no statistically significant differences in the percentages of au-tomatic message leaving,inconvenient answering,resident death,family members unable to answer and number error between the two groups(P＞0.05),and there was no statistical significance in the distribution of disconnected calls between the two groups(P＞0.05).In the effective follow-up calls,there was no statistical significance in the answers to questions related to hypertension and diabetes,compliance and exercise between the two groups(P＞0.05).The average call duration in the intel-ligent group was significantly shorter,and follow-up satisfaction was lower than that in the control group(P＜0.05).Conclusion Intelligent voice follow-up system can replace manual telephone follow-up to a certain extent,and help medical staff understand the compliance of home blood pres-sure,blood sugar,medication,exercise and secondary prevention in IS patients,and can save fol-low-up time and improve follow-up efficiency compared with manual follow-up,but its language rec-ognition and improvement of cooperation rate still need to be optimized.

Objective To analyze the application of intelligent speech follow-up system in sec-ondary prevention of ischemic stroke(IS).Methods A total of 842 IS patients who received intra-venous thrombolysis were randomly divided into intelligent group and artificial group.In the artificial group,corresponding intelligent follow-up templates were developed for the main risk factors affecting the occurrence of IS.The intelligent follow-up system determined the follow-up time and period ac-cording to the reserved information of patients when they were discharged,automatically called out the patients'home conditions for follow-up,and converted the response contents into text mode for out-put.The artificial group was followed up by professionally trained nursing staff,and the follow-up con-tent was the same as that of the intelligent group.Call out,hypertension,diabetes,medication,exer-cise,average call time and satisfaction of follow-up in the two groups were collected.Results The tel-ephone connection rates showed no statistical significances between two groups(P＞0.05).During the follow-up calls,the correct recognition rate of follow-up contents in the intelligent group was low-er,and therateof unwillingness to cooperate and call interruption rate were higher than those in the control group(P＜0.05).There were no statistically significant differences in the percentages of au-tomatic message leaving,inconvenient answering,resident death,family members unable to answer and number error between the two groups(P＞0.05),and there was no statistical significance in the distribution of disconnected calls between the two groups(P＞0.05).In the effective follow-up calls,there was no statistical significance in the answers to questions related to hypertension and diabetes,compliance and exercise between the two groups(P＞0.05).The average call duration in the intel-ligent group was significantly shorter,and follow-up satisfaction was lower than that in the control group(P＜0.05).Conclusion Intelligent voice follow-up system can replace manual telephone follow-up to a certain extent,and help medical staff understand the compliance of home blood pres-sure,blood sugar,medication,exercise and secondary prevention in IS patients,and can save fol-low-up time and improve follow-up efficiency compared with manual follow-up,but its language rec-ognition and improvement of cooperation rate still need to be optimized.

Objective To evaluate the association between hypersensitive C reactive protein (hs-CRP) and the incidence of acute kidney injury in subarachnoid hemorrhage(SAH) patients.Methods It retrospectively recruited 213 cases of computerized tomography validated SAH patients from the neurology ICU from Beijing Tiantan Hospital between January 2012 and January 2015.The average age was (56.29±11.95) years old,and the patients were divided into AKI and non-AKI groups according to Kidney Disease: Improving Global Outcomes (KDIGO) diagnosis standards, Clinical features of AKI and Non-AKI patients including serum levels of hs-CRP were compared and multi-logistic regression was applied to find the risk factors concerning with the incidence of AKI.Receiver operating characteristics (ROC) curve was also plotted to evaluate the diagnostic value of hs-CRP towards the incidence of AKI.Results A total of 25 (11.74%) patients developed AKI.Average age of the SAH patients in both AKI and non-AKI groups were (63.60±12.21) years old vs.(55.31±11.60) years old(t=-3.33, P<0.05).The ratios of diabetics were were 28.00% vs.11.17% (χ2=5.47,P<0.05) and the ratio of proteinuria were 80.00% vs.34.57%, respectively (χ2=3.83, P<0.05).The median of serum creatinie were 63.72(51.45, 79.72)μmol/L vs.53.21(45.27, 65.62)μmol/L (P<0.05), and serum hs-CRP were (14.12±5.03)mg/L vs.(10.23±6.76)mg/L (P<0.05), and the ratios of antibiotics application were 84.00% vs.43.08% (P<0.05 for all).Multi-logistic regression analysis showed that serum hs-CRP was an independent risk factors for AKI after age, serum creatinine at admission were adjusted.[OR (95% CI) was 3.33(1.13, 9.85),P<0.05 for all].The area under curve of ROC was 0.69 (P<0.05), and the cut-off point of serum hs-CRP under the maximum Youden index was 13.85 mg/L.Conclusion Serum hs-CRP is an independent risk factor of theincidence of AKI in SAH patients, the significantly increase of serum hs-CRP might be an important predictor of the incidence of AKI in SAH patients.