Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Good endometrial receptivity is an essential factor for embryo implantation,and gene expression in endometrial tissue during the window of implantation(WOI)is closely related to receptivity.Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases,as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression.Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism.Moreover,gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure,thereby guiding individualized embryo transfer strategies.This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions.This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level,in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To explore the Helicobacter pylori (Hp) infection rate and antibody typing of 1111 physical examination people in plateau area, and to analyze the risk factors of Hp infection by logistics regression analysis. Methods 1111 healthy people with physical examination in plateau area from January 2022 to December 2022 were selected as the research subjects. The Hp infection rate and antibody typing were calculated, and the risk factors of Hp infection were analyzed by logistics regression analysis. Results The Hp infection rate of physical examination people in plateau area was 62.47% (694/1 111). The infection rate of type I HP in infected patients was higher than that of type Ⅱ HP(75.50% vs 24.50%) (χ²=361.141, P<0.001). The AUC of CagA in the diagnosis of Hp infection was higher than that of antibody VacA or Ure positive diagnosis alone (Z=6.740, 7.608, P<0.001). The proportions of people with male gender, often eating pickled or barbecued foods, history of chronic gastric disease and family members living together≥4 in infected group were higher than those in uninfected group (χ²=4.418, 8.708, 16.565, 32.583, P=0.036, 0.003, <0.001, <0.001) while the proportion of people with regular garlic consumption was lower than that in uninfected group (χ²=5.153, P=0.023). Often eating pickled or barbecued foods [OR (95%CI)=2.038 (1.049-3.961)], history of chronic gastric disease [OR(95%CI)=1.706 (1.132-2.569)] and family members living together≥4 [OR (95%CI)=1.857 (1.135-3.037)] were risk factors of Hp infection, and regular garlic consumption [OR (95%CI)=0.559 (0.346-0.903)] was a protective factor (P=0.036, 0.011, 0.014, 0.018). Conclusion The Hp infection rate and antibody Ure positive rate are higher in physical examination people in plateau area, and chronic gastric disease history and often eating pickled or barbecued foods are risk factors of Hp infection.

Protein phosphorylation modification is one of the key regulatory mechanisms in cellular signaling transduction and metabolic processes. The phosphorylation state of target proteins is regulated by specific protein kinases and phosphatases, which add or remove phosphate groups. Histidine phosphorylation (pHis) plays a crucial role in both prokaryotes and eukaryotes life activities and is linked to various pathological processes. Unlike the stable phosphorylation of proteins via phosphate ester bonds, histidine phosphorylation is linked through phosphoramide bonds, making it highly sensitive to high temperatures and low pH. This sensitivity has historically impeded progress in identifying and studying histidine phosphorylation. In recent years, the development of new techniques in phosphoproteomics and the emergence of pHis-specific antibodies have promoted the identification and functional research of pHis-modified substrates. For the first time, more than 700 pHis-modified proteins have been identified in mammalian cells, and pHis-modified substrates such as focal adhesion kinase (FAK) and phosphoglycerate mutase 1 (PGAM1) have been found to promote tumor development. This article mainly reviewed the key mechanisms and functions of histidine kinases and histidine phosphatases in regulating the histidine phosphorylation of specific substrates, and highlights their significant roles in human physiological and pathological processes, aiming to provide guidance for further research into the biological functions of histidine phosphorylation.

OBJECTIVE: To study the effect of propofol used for painless gastroscopy and colonoscopy on psychomotility recovery. METHODS: One hundred adult patients undergoing painless gastroscopy and colonoscopy were recruited, aged 18-72 years, with American Society of Anesthesiologist (ASA) physical status Ⅰ-Ⅱ. According to age, the patients were divided into youth group (20-39 years old, 27 cases), middle age group (40-54 years old, 37 cases), and elder group (55-64 years old, 36 cases). Propofol was continuously infused according to the patients' condition to mantain the bispectal index (BIS) score 55-64. All the patients received psychomotility assesment 30 min before the operations when the discharge criteria were met including number cancellation test, number connection test and board test. The heart rate, blood pressure, saturation of pulse oximetry, electrocardiograph and BIS were monitored during the operation. The operating time, recovery time, total volume of propofol and discharge time were recorded. If the results obtained were inferior to those before operation, a third assessment was taken 30 minutes later until the results recovered or being superior to the baseline levels. RESULTS: All the patients completed the first and second assessments, and 25 patients had taken the third assessment. There was no statistically significant difference in the results of psychomotility assessment when the patients met the discharge standard. Furthermore, the results were analyzed by grouping with age, and there was no statistical difference in the test results of the youth and middle age groups compared with the preoperative group, among which, the efficiency of the number cancellation test was significantly better than that before operation in the youth group (P < 0.05). However, in the elderly patients the number cancellation efficiency, number connection test and board test were significantly inferior to that before operation (P < 0.05). There was no significant difference in the accuracy of number cancellation compared with that before operation. The patients who needed the third test in the elder group were significantly more than in the other groups (P < 0.05). Compared with the preoperative results, there was no statistical difference in the test results of those who completed the third test. CONCLUSION The psychomotility function of the patients who underwent painless gastroscopy and colonoscopy was recovered when they met discharge criteria. The elderly patients had a prolonged recovery period.
Adult ; Aged ; Middle Aged ; Adolescent ; Humans ; Young Adult ; Propofol ; Hypnotics and Sedatives ; Gastroscopy/methods* ; Conscious Sedation/methods* ; Colonoscopy/methods*