Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Objective To investigate and analyze epidemiological characteristics of patients with mycoplasma pneumoniae pneumonia (MPP) from 2020 to 2023, and the risk factors for plastic bronchitis (PB), To provide data support for developing preventive measures. Methods The medical records of 2 257 patients with respiratory tract infection treated at Huai'an Hospital Affiliated to Xuzhou Medical University from 2020 to 2023 were collected. Count the number of MPP patients and analyze the MP detection rate. Multivariate logistic regression analysis and ROC curve was used to screen the risk factors for PB. Results A total of 858 cases were positive for MP antibodies, and the detection rate was 38.02%. There are statistically significant differences in MP detection rates among different genders, age groups, and years (P<0.05). Among the 286 patients diagnosed with MPP and undergoing bronchoscopy, 68 (23.78%) patients had PB. According to univariate and multivariate logistic regression analysis, small age, higher N%, D-D, LDH and AST levels were independent risk factors for PB (P<0.05). ROC curve analysis shows that age and combined detection are the most effective indicators for PB prediction, with areas under the curve of 0.998 and 0.961, respectively. Conclusion MP is the main pathogen of respiratory tract infections in the area from 2020 to 2023. Women and children are more susceptible to MP infection. Small age, high N%, DD, LDH and AST levels are independent risk factors for PB in patients with MPP. Targeted preventive measures should be taken for MP susceptible population, and close attention should be paid to PB related risk factors to prevent disease progression and the occurrence of PB.

The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic ADs, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and ADs. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.
Humans ; Lupus Erythematosus, Systemic/immunology* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; Cell- and Tissue-Based Therapy/methods* ; Animals ; T-Lymphocytes/immunology*

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

From the perspective of competitive endogenous RNA(ceRNA) constructed by metastasy-associated lung adenocarcinoma transcript 1(Malat1) and microRNA 16-5p(miR-16-5p), the improvement mechanism of Tonggu Xiaotong Capsules(TGXTC) on the imbalance and disorder of "cholesterol-iron" metabolism in chondrocytes of osteoarthritis(OA) was explored. In vivo experiments, 60 8-week-old C57BL/6 mice were acclimatized and fed for 1 week and then randomly divided into two groups: blank group(12 mice) and modeling group(48 mice). The animals in modeling group were anesthetized by 5% isoflurane inhalation, which was followed by the construction of OA model. They were then randomly divided into model group, TGXTC group, Malat1 overexpression group, and TGXTC+Malat1 overexpression(TGXTC+Malat1-OE) group, with 12 mice in each group. The structural changes of mouse cartilage tissues were observed by Masson staining after the intervention in each group. RT-PCR was employed to detect the mRNA levels of Malat1 and miR-16-5p in cartilage tissues. Western blot was used to analyze the protein expression of ATP-binding cassette transporter A1(ABCA1), sterol regulatory element-binding protein(SREBP), cytochrome P450 family 7 subfamily B member 1(CYP7B1), CCAAT/enhancer-binding protein homologous protein(CHOP), acyl-CoA synthetase long-chain family member 4(ACSL4), and glutathione peroxidase 4(GPX4) in cartilage tissues. In vitro experiments, mouse chondrocytes were induced by thapsigargin(TG), and the combination of Malat1 and miR-16-5p was detected by double luciferase assay. The fluorescence intensity of Malat1 in chondrocytes was determined by fluorescence in situ hybridization. The miR-16-5p inhibitory chondrocyte model was constructed. RT-PCR was used to analyze the levels of Malat1 and miR-16-5p in chondrocytes under the inhibition of miR-16-5p. Western blot was adopted to analyze the regulation of TG-induced chondrocyte proteins ABCA1, SREBP, CYP7B1, CHOP, ACSL4, and GPX4 by TGXTC under the inhibition of miR-16-5p. The results of in vivo experiments showed that,(1) compared with model group, TGXTC group exhibited a relatively complete cartilage layer structure. Compared with Malat1-OE group, TGXTC+Malat1-OE group showed alleviated cartilage surface damage.(2) Compared with model group, TGXTC group had a significantly decreased Malat1 mRNA level and an increased miR-16-5p mRNA level in mouse cartilage tissues(P<0.01).(3) Compared with the model group, the protein levels of ABCA1 and GPX4 in the cartilage tissue of mice in the TGXTC group increased, while the protein levels of SREBP, CYP7B1, CHOP and ACSL4 decreased(P<0.01). The results of in vitro experiments show that,(1) dual-luciferase was used to evaluate that miR-16-5p has a targeting effect on the Malat1 gene.(2)Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group had an increased mRNA level of miR-16-5p and an decreased mRNA level of Malat1(P<0.01).(3) Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group exhibited increased expression of ABCA1 and GPX4 proteins and decreased expression of SREBP, CYP7B1, CHOP, and ACSL4 proteins(P<0.01). The reasults showed that TGXTC can regulate the ceRNA of Malat1 and miR-16-5p to alleviate the "cholesterol-iron" metabolism disorder of osteoarthritis chondrocytes.
Animals ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Chondrocytes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Osteoarthritis/drug therapy* ; Iron/metabolism* ; Male ; Cholesterol/metabolism* ; Humans ; Capsules ; RNA, Competitive Endogenous