BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

OBJECTIVE: To investigate the clinical efficacy of lengthened proximal femoral nail antirotation (PFNA) and InterTan in the treatment of subtrochanteric femur fractures in the elderly. METHODS: A retrospective analysis was performed on the data of 65 elderly patients diagnosed with subtrochanteric femoral fractures who met the inclusion criteria between October 2016 and January 2022. The enrolled patients were categorized into two groups according to the type of internal fixation used: the lengthened proximal femoral nail antirotation(PFNA) group and the InterTan group. There were 32 patients in the PFNA group, comprising 20 males and 12 females, with ages ranging from 60 to 85 years old with an average of (69.3±6.7 ) years old. Among these patients, 15 patients resulted from traffic accidents and 17 patients were caused by falls. According to the Seinsheimer classification system, there were 11 patients as type Ⅱ, 14 patients as type Ⅲ, 6 patients as type Ⅳ, and 1 patient as type Ⅴ. The InterTan group comprised 33 patients, including 20 males and 13 females, aged from 60 to 85 years old with an average of (69.8±7.8 ) years old. Of these, 15 patients resulted from traffic accidents, while 18 patients were caused by falls. According to the Seinsheimer classification system, 10 patients as type Ⅱ, 15 patients as type Ⅲ, 7 patients as type Ⅳ, and 1 patient as type Ⅴ. The intraoperative blood loss, operative duration, and fracture healing time were recorded and compared between two groups. The quality of fracture reduction was assessed using Chang's criteria. Additionally, the Harris hip score was utilized to evaluate hip function in both groups at 3 months postoperatively and at the final follow-up. RESULTS: All patients were followed up for a period ranging from 10 to 20 months with an average of (14.6±4.5) months. No statistically significant differences were observed between two groups in terms of operation time, intraoperative blood loss, quality of fracture reduction, or reduction methods (P>0.05). Three months after the surgery, the Harris hip score in the InterTan group was 80.0(78.0, 83.5) points, which was significantly higher than that in the PFNA group, which recorded a score of 77.5(75.0, 81.8) points. This difference was statistically significant (P<0.05). At the final follow-up, the Harris hip score in the InterTan group was 80.0(76.5, 87.0), while that in the PFNA group was 78.0(74.3, 82.8). No statistically significant difference was observed between two groups (P>0.05). CONCLUSION The use of lengthened PFNA and InterTan in the treatment of elderly subtrochanteric femur fractures can both achieve good treatment results, with the advantages of simple operation, firm fixation, and low failure rate of internal fixation. The lengthened InterTan can achieve better hip function than PFNA.
Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Bone Nails ; Retrospective Studies ; Hip Fractures/surgery* ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/methods* ; Femoral Fractures/surgery*

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by in vitro cytotoxicity and in vivo biosafety. First, we characterized the chemical composition of the cationic lipid peptides by nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) and time-of-flight mass spectrometry (MS). The results of particle size and potential tested by dynamic light scattering particle size analysis showed that at a nitrogen/phosphorus (N/P) ratio of 20, the RLS/mRNA composite assemblies formed homogeneous nanoparticles with an average particle size of about 220 nm and a surface ζ potential of about +21 mV. In vitro gene transfection, the transfection experiments demonstrated that RLS exhibited 1.2-fold higher transfection efficiency in human embryonic kidney 293 cells (HEK293) and 3-fold higher transfection efficiency in rat mesenchymal stem cells (MSC) compared to Lipofectamine 2000. In addition, after microinjection of RLS into zebrafish embryos, we evaluated the survival, hatching, and teratogenicity rates, all of which confirmed its favorable in vivo safety profile. Thus, this amphiphilic cationic lipid peptide RLS, enriched with branched arginine, exhibits excellent mRNA delivery properties and safety. These findings highlight its potential as a promising gene therapy tool.