Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

Objective: To explore the results of comprehensive geriatric assessment (CGA) among convalescent elderly population, so as to provide the basis for strengthening the health management service level for convalescent elderly population. Methods: A total of 200 elderly people who convalesced at Hangzhou Wuyunshan Hospital from January 2021 to December 2023 were selected as the research subjects. The basic information, physical condition, psychological status, functional status, and social environment of the elderly were investigated using the CGA protocol. The basic characteristics of the elderly, physical conditions such as medication adherence, pain, malnutrition and frailty, psychological conditions such as cognitive function, anxiety symptoms and depression symptoms, functional conditions such as fall risk and social support level and social environment assessment results were analyzed. Results: Among the 200 elderly individuals, 58.00% were male, 44.50% were aged 70 to <80 years, 58.00% had an education level of high school or above, 55.00% were unmarried, 61.50% were childless, and 60.50% had basic medical insurance for employees. In terms of physical condition, 59.00% had comorbid chronic diseases, 40.50% used multiple medications, and the incidences of poor medication adherence, pain, malnutrition, and frailty were 22.50%, 10.00%, 54.00%, and 36.00%, respectively. Regarding psychological status, the incidences of impaired cognitive function, anxiety symptoms, and depressive symptoms were 57.00%, 89.50%, and 91.00%, respectively. In terms of functional status and social environment, 90.00% had a risk of falling, and 31.00% had a high level of social support. Univariable analysis showed that elderly individuals aged ≥80 years and those with an education level of primary school or below had higher incidences of poor medication adherence during convalescence; elderly individuals with poor medication adherence had a higher incidence of pain; and elderly individuals with impaired cognitive function, anxiety symptoms, and depressive symptoms had higher incidences of malnutrition (all P<0.05). Conclusions The physical condition and psychological status of convalescent elderly individuals are relatively poor, with a high risk of falling and insufficient levels of social support. Poor medication adherence is associated with advanced age and lower education levels, while malnutrition is associated with impaired cognitive function, anxiety symptoms, and depressive symptoms. Comprehensive health management for convalescent elderly population should be strengthened, and personalized health management services should be provided to improve their quality of life and sense of well-being.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

This study investigated the functions and regulatory mechanism of Portulacae Herba and its chemical components on the Toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MyD88)/nuclear factor kappa B(NF-κB) inflammatory signaling pathway in the colon tissue of mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC). A total of 35 mice were randomly divided into groups, including a blank group, a model group, a mesalazine group(0. 5 g·kg~(-1)), and low, medium,and high dose alkaloids from Portulacae Herba groups(9, 18, 36 mg·kg~(-1)), and a combination treatment group, with 5 mice in each group. The blank group was given purified water, while the other groups were continuously given a 3% DSS solution for 7 days to induce the UC model. From day 8 onwards, the treatment group received oral gavage according to the prescribed doses for 14 days. The overall condition, body weight, stool characteristics, and presence of blood in the stool were recorded daily. After the experiment, the disease activity index(DAI) was assessed for each group, and colon length was measured. Histopathological changes in colon tissue were examined using hematoxylin-eosin(HE) staining. The levels of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α),and interleukin-1β( IL-1β) in serum were measured by enzyme-linked immunosorbent assay( ELISA). The protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were measured using Western blot and quantitative real-time PCR(qPCR).Compared to the blank group, the model group showed a significant decrease in body weight, a notable increase in DAI scores, a significant shortening of colon length, and evident histopathological damage. The levels of inflammatory cytokines TNF-α and IL-1β in the serum were significantly elevated, and the protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were significantly up-regulated. In contrast, the alkaloids from Portulacae Herba treatment groups significantly improved symptoms and reduced body weight loss in mice, decreased DAI scores, alleviated colon shortening, lowered serum levels of TNF-α and IL-1β,significantly down-regulated the expression levels of TLR4, MyD88, and NF-κB proteins and genes in colon tissue, as well as reduced histopathological damage. Therefore, the study suggests that alkaloids from Portulacae Herba can alleviate intestinal inflammation damage in DSS-induced UC mice, with its mechanism involving the TLR4/MyD88/NF-κB signaling pathway.
Animals ; Colitis, Ulcerative/immunology* ; Toll-Like Receptor 4/immunology* ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Male ; Alkaloids/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Female ; Colon/metabolism* ; Disease Models, Animal

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*