OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Glucose transporters (GLUTs) are pivotal membrane proteins that facilitate the passive transport of glucose into cells. However, their aberrant overexpression is closely linked to the Warburg effect and chemotherapy resistance of tumors. GLUTs are complex multi-pass transmembrane proteins that require detergents for extraction from the cell membrane during preparation. The persistent presence of detergents in the sample can disrupt lipid-protein interactions, potentially leading to conformational distortion and functional losses of GLUTs, severely hindering the research into their structures and transport mechanisms. To eliminate detergent interference and preserve its authentic conformation, this study employs nanodisc technology and utilizes the self-assembly of the membrane scaffold protein MSP1E3D1 and phospholipids to produce a biomimetic membrane environment, thereby overcoming the limitations of conventional methods. The C-terminal His10-tagged GLUT1 was heterologously expressed in the insect cell Sf9/Bac-to-Bac system, and the GLUT1-nanodisc complex was obtained after detergent solubilization, affinity chromatography purification via anti-His antibody resin, and self-assembly. The successfully reconstituted nanodisc complex was further purified by Ni-NTA affinity chromatography. Nanodisc reconstitution produced monodisperse GLUT1 particles that retained native secondary structure, as confirmed by far-UV circular dichroism (CD) spectroscopy and dynamic light scattering (DLS). Unlike conventional detergent micelles, which lack a true lipid bilayer, distort transmembrane-helix topology, and occlude ligand-binding sites, the nanodisc platform embeds GLUT1 in a phospholipid bilayer that preserves its authentic conformation while eliminating detergent interference. The resulting GLUT1-nanodisc complex is therefore a superior scaffold for high-resolution cryo-EM structural analysis, permitting detailed interrogation of the transporter's conformational cycle, its interactions with partner proteins, and downstream structure-guided, high-throughput drug screening.
Nanostructures/chemistry* ; Glucose Transporter Type 1/biosynthesis* ; Humans ; Animals ; Phospholipids/chemistry* ; Detergents/chemistry*

Intervertebral disc degeneration(IDD) is the pathological basis of spinal diseases. With the development and change of working and living style, IDD gradually presents the trend of younger in recent years. The effective prevention and treatment of IDD has become a hotspot in clinical research. Recent studies have shown that oxidative stress plays an important role in IDD. The disruption of reactive oxygen species balance in cells or the body leads to changes in extracellular matrix and intervertebral disc cell phenotype, which induces oxidative stress of intervertebral disc and leads to IDD. Oxidative stress can affect the development of IDD through apoptosis, autophagy, senescence and extracellular matrix of intervertebral disc. Currently, opioids and drugs for promoting blood circulation and pain relief are commonly used in clinical treatment of IDD, which can alleviate some symptoms to a certain extent, but is easy to induce gastrointestinal and other adverse reactions. Meanwhile, due to the long treatment cycle and poor patient compliance to a certain extent, which brings great difficulties to the treatment. At the same time, traditional Chinese medicine plays an important role in the treatment of IDD due to its advantages of low cost and fewer adverse reactions. With the in-depth research of modern technologies such as molecular biology and network pharmacology, it has been found that traditional Chinese medicine can intervene in the expression of oxidative stress-related functions, namely, slowing down apoptosis, autophagy and degradation of extracellular matrix, etc, to play a role in the treatment of IDD. In this paper, the role of oxidative stress in IDD and the research results on the intervention of traditional Chinese medicine in oxidative stress will be expounded, in order to provide reference for the prevention and treatment of IDD by traditional Chinese medicine.

Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.

Background: Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. Methods: We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). Results: Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05). Conclusion Although the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.

OBJECTIVE： To establish a method for the determination of piperitylmagnolol in the incubation system of liver microsomes， and to investigate the metabolic characteristics of it in different species of liver microsomes. METHODS： The piperitylmagnolol were respectively dissolved in NADPH activated liver microsome incubation systems of human， rat， mouse， monkey and dog， and then incubated in water at 37 ℃. The reaction was terminated with methanol at 0， 2， 5， 10， 15， 20， 30， 45 and 60 minutes of incubation， respectively. Using magnolol as internal standard， UPLC-MS/MS method was used to determine the concentration of piperitylmagnolol in the incubation system. The determination was performed on Acquity UPLCTM CSH C18 column with mobile phase consisted of 0.1％ formic acid-methanol （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃， and the sample size was 2 μL. The ion source was electrospray ion source， and the positive ion scanning was carried out in the multiple reaction monitoring mode. The ion pairs used for quantitative analysis were m/z 401.2→331.1 （piperitylmagnolol） and m/z 265.1→247.0 （internal standard）， respectively. Using the concentration of piperitylmagnolol at 0 min of incubation as a reference， the residual percentage， metabolism half-life in vitro （t1/2） and intrinsic clearance （CLint） were calculated for different incubation systems. The metabolic pathway of piperitylmagnolol was studied by chemical inhibitor method. Under the above chromatographic conditions， the metabolites in vitro were preliminarily analyzed by first-order full scanning and positive ion detection. RESULTS： The linear range of piperitylmagnolol was 3.91-500.00 ng/mL. The limit of quantitation was 3.91 ng/mL. RSDs of intra-day and inter-day were less than 10％. The accuracy ranged 87.40％-103.75％. Matrix effect didn’t affect the determination of the substance to be measured. The piperitylmagnolol was metabolized significantly in human， rat， mouse and dog liver microsomes， but not in monkey liver microsomes. After incubating for 30 min， residual percentage of piperitylmagnolol kept stable in different species of liver microsomes. The t1/2 of piperitylmagnolol were 12.07， 17.68， 17.59， 216.56 and 61.88 min in human， rat， mouse， monkey and dog liver microsomes； CLint were 0.115， 0.078， 0.079， 0.006， 0.022 mL/（min·mg）， respectively. Inhibitory rates of CYP2A6， CYP2D6， CYP2C19， CYP3A4， CYP2C9， CYP2E1 and CYP1A2 to compound metabolism were 55.76％， 93.94％， 96.01％， 93.69％， 71.81％， 23.25％， 28.04％， respectively. Quasi-molecular ion peaks of the two main metabolites of piperitylmagnolol in human liver microsomes were m/z 441.2（[M+Na]+） and m/z 337.2（[M+H]+）， respectively. CONCLUSIONS： Established UPLC-MS/MS method is simple， rapid and specific， and can be used for the determination of piperitylmagnolol concentration in the incubation system of liver microsomes and pharmacokinetic study. The metabolic characteristics of the compound are different among liver microsomes of human， rat， mouse， monkey and dog. Its metabolism process may be associated with CYP2D6， CYP2C19， CYP3A4， CYP2C9， etc.

In order to explore the regulation mechanisms of follicular helper T cell (Tfh Cell) differentiation,optimized conditions of in vitro induction from both peripheral blood mononuclear cells and MAC sorted Na(i)ve CD4 + T cells to human Tfh cells were developed.Induction efficiency difference of TCR signal anti-hCD3e stimulation between coated on solid phase and in soluble phase was also determined.Differentiation efficiency of CD4 + CXCR5 + ICOS+PD-1 + Tfh cell was determined by FACS while the expression level of IL-21 in cell supernatant was determined by ELISA tests.An ultimate induction condition that 5 μg/mL coated overnight anti-hCD3e stimulated na(i)ve CD4 + T cells to differentiate into Tfh at an up to 20.4％ percentage was finally determined.The optimization of in vitro induction protocol of human Tfh provided an effective examine platform for the studies on Tfh differentiation mechanisms and related pharmacology,toxicity and metabolic experiments.