Salvia miltiorrhiza is a perennial herb of the genus Salvia(Lamiaceae). As one of the earliest medicinal plants to undergo molecular biology research, it has gradually become a model plant for molecular biology of medicinal plants. With the gradual analysis of the genome of S. miltiorrhiza and the biosynthetic pathways of its main active components tanshinone and salvianolic acids, the transcriptional regulation mediated by transcription factors and related regulatory proteins has gradually become a new research focus. Due to the lack of scientific and unified naming of transcription factors and different research indexes in different literature, this paper systematically sorted out the transcription factors in different literature with the genomes of DSS3 from selfing for three generations and bh2-7 from selfing for six generations as reference. In total, 73 transcription factors and related regulatory proteins belonging to 13 gene families were identified. The effects of overexpression or gene silencing experiments on tanshinone and salvianolic acids were also analyzed. This study unified the identified transcription factors, which laid a foundation for further constructing the regulatory networks of secondary metabolites and insect or stress resistance and improving the quality of medicinal materials by using global transcriptional regulation engineering.
Salvia miltiorrhiza/chemistry* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Abietanes/metabolism*

OBJECTIVE: To explore serological detection and blood transfusion strategies of mimicking antibodies, so as to provide appropriate transfusion strategies. METHODS: Detailed serological tests, including ABO blood group, Rh typing, antibody specificity, etc,were performed on two patients with autoimmune hemolytic anemia(AIHA). Meanwhile, the references about blood transfusion from mimicking antibody patients published from 1977 to 2024 in China and abroad were retrospectively summarized and analyzed. RESULTS: The patient 1 blood type was AB,CCDee and the antibody is mimicking anti-e, transfusion the e-negative red blood cells (RBCs) was effective. After two transfusions of e-RBCs, hemoglobin levels significantly increased from 48 g/L to 91 g/L, with complete resolution of hemolytic symptoms. The patient 2 blood type was O,CcDee, and the antibody was mimicking anti-c, the patient was diagnosed with AIHA and treated with hormone. No blood products were transfused during hospitalization, and his hemolysis was relieved. CONCLUSION Strictly grasping the indication of blood transfusion, blood transfusion should not be performed in the unnecessary conditions, and the corresponding antigen-negative RBC should be screened for transfusion in the necessay conditions.
Humans ; Blood Transfusion ; Anemia, Hemolytic, Autoimmune/therapy* ; ABO Blood-Group System ; Retrospective Studies ; Antibodies ; Male ; Blood Grouping and Crossmatching

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To explore the clinicopathological characteristics,prognosis and influencing factors of different pathological subtypes of gastric signet ring cell carcinoma(GSRC).Methods A retrospective analysis was performed on the clinical data of 232 patients with GSRC collected from January 2016 to December 2018 in Lanzhou University Second Hospital.According to the WHO classification criteria for GSRC,the patients were divided into pure gastric signet-ring cell carcinoma(pGSRC,n=36)and mixed gastric signet-ring cell carcinoma(mGSRC,n=196).The follow-up as of September 30,2022,the survival analysis was done using Kaplan-Meier method,the univariate and multivariate Cox regression were performed to analyze the risk factors affecting the prognosis of GSRC patients.Results The median survival time of pGSRC and mGSRC patients was 41.0(6.0-70.0)months and 24.0(2.0-74.0)months,respectively.Kaplan-Meier analysis showed that combination with diabetes,anemia,tumor diameter,nerve invasion,lymphovascular invasion,T stage,N stage,GSRC pathological subtype,CA125 and tumor diameter could affect the overall survival(OS)of patients with GSRC after radical gastrectomy(P＜0.05),but Her-2,whether adjuvant chemotherapy or not and others elements had no significant effect on OS of GSRC patients after radical gastrectomy(P＞0.05).Univariate Cox regression analysis showed that the combination with diabetes(P=0.031),anemia(P=0.028),tumor diameter＞5 cm(P=0.009),nerve invasion(P=0.002),lymphovascular invasion(P=0.002),mGSRC pathological type(P=0.039),T2-T4 stage(P=0.001),N1-N4 stage(P=0.004),pTNM stage Ⅲ(P=0.044),the number of lymph node metastasis＞30(P=0.044)and CA125 positive(P=0.009)were related to the prognosis of patients with GSRC after radical gastrectomy.Multivariate Cox regression analysis showed that mGSRC pathological type(P=0.035),T2-T4 stage(P=0.003),CA125 positive(P=0.010)were independent risk factors for poor prognosis of patients with GSRC after radical gastrectomy.Conclusion Compared with pGSRC,patients with mGSRC at diagnosis have higher pTNM stages,more aggressive,and shorter median survival time.mGSRC pathological type,T2-T4 stage,and CA125 positive were all independent factors affecting the prognosis of patients with GSRC.

Objective To investigate the biocompatibility of new gadolinium-doped hydroxyapatite(Gd-HA)composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation.The experiment was divided into three groups,the HA group,the Gd-HA group,and the control group.Rabbit adipose-derived mesenchymal stem cells(ADSCs)were isolated,cultured and characterized,and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system.Cell survival and cytotoxicity were assessed by live-dead cell staining,cell proliferation ability within the scaffolds was assessed by CCK-8 assay,and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation.The toxic reactions of the scaffold materials were observed by skin irritation test,systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.Results The Gd-HA composite scaffold showed irregular void structure under electron microscope.Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped.The positivity rate of CD29 was 96.94％,CD44 was 97.90％,CD45 was 0.10％,and CD34 was 0.46％,which was obtained using flow cytometry.Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA)group after 5 days of co-culture.CCK-8 assay showed no significant difference in cell proliferation within 0-3 days.After 3 days,the Gd-HA group was significantly better than the HA group and the control group(P＜0.05).Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups,showing a deeper red color.No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin.The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity,and the body mass tended to increase steadily(P＞0.05).HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group,and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time.At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue,and no pathological changes were observed in the HE staining of liver and kidney at the 12th week.Conclusion Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation,and they are expected to serve as good carriers for stem cell transplantation in tissue engineering.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

Objective:To explore the changes in resting energy expenditure (REE) values in patients with severe burns under different metabolic stages and the selection of the optimal calculation formula.Methods:This study was a retrospective and observational study. From April 2020 to December 2023, 40 patients (32 males and 8 females, aged (54±17) years) with severe burns meeting inclusion criteria were treated in the Second Affiliated Hospital of Zhejiang University School of Medicine. After admission, the patients were given routine clinical treatments such as sedation and analgesia, debridement, and skin grafting. At 3, 5, 7, 9, 11, 14 days after injury and every 7 days thereafter, the REE values (i.e., REE measured values) were measured by indirect calorimetry in patients with severe burns who met the measurement conditions till the patients recovered or died. On the day the patient's REE was measured, Milner, Hangang, the Third Military Medical University, Carlson, and Peng Xi team's linear formula were used respectively to calculate the REE value (i.e., REE formula values). The post-injury time to measure REE in patients was calculated, and the clinical characteristics of patients in acute inhibition, hypermetabolic, metabolic balance, and metabolic remodeling phases were compared. The REE measured values and the difference between the REE formula values and the REE measured values of patients under the 4 different metabolic phases were calculated.Compared with the REE measured values, the 10% accuracy rate and 20% accuracy rate were calculated to evaluate the accuracy of the REE formula values. The absolute percentage error (APE) of the REE formula values were calculated to evaluate the deviation. The metabolic formula (i.e., the optimal calculation formula) that was closest to the measured REE values was screened out, and further exploration was conducted to identify the key factors that affected the accuracy of the optimal calculation formula under different metabolic phases.Results:The post-injury time to measure REE in patients with severe burns was (40±19) days. Comparisons showed that under the 4 different metabolic phases, patients in the metabolic remodeling phase had the highest age, height, weight, body mass index, total body surface area. Age in the metabolic remodeling phase was significantly higher than that in the acute inhibition and hypermetabolic phases (with t values of -3.02 and -4.20, respectively, with all P values <0.05), weight was significantly higher than that in the hypermetabolic and metabolic balance phases (with t values of -1.97 and -2.61, respectively, with all P values <0.05), body mass index was significantly higher than that in the hypermetabolic phase ( t=-2.90, P<0.05), and total body surface area was significantly larger than that in the hypermetabolic and metabolic balance phases (with t values of -2.02 and -2.27, respectively, with all P values <0.05). There was no significant change in patients' REE measured values under the 4 different metabolic stages ( P>0.05). Except for the Peng Xi team's linear formula ( P>0.05), the difference between REE measured values and REE formula values calculated by using Milner, Hangang, the Third Military Medical University, and Carlson formulas respectively was statistically significant under different metabolic stages (with H values of 14.50, 27.15, and 37.26, respectively, F=11.80, P<0.05). Comprehensive analysis of 10% accuracy, 20% accuracy, and APE showed that in the acute inhibition phase, the REE formula values calculated by Peng Xi team's linear formula was closest to REE measured values, and the APE of the REE formula values calculated by Peng Xi team's linear formula was significantly lower than those calculated by Milner formula, Hangang formula, the Third Military Medical University formula, and Carlson formula (with t values of 9.00, -2.10, 5.95, and 6.68, respectively, with all P values <0.05). In the hypermetabolic phase, the REE formula values calculated by Hangang formula were closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by using Milner formula, the Third Military Medical University formula, Carlson formula, and Peng Xi team's linear formula (with t values of 10.20, 10.33, 10.65, and 5.87, respectively, with all P values <0.05). In the metabolic balance phase, the REE formula values calculated by Hangang formula were again closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by Milner formula, the Third Military Medical University formula, and Carlson formula (with t values of 7.11, 8.52, and 8.60, respectively, with all P values <0.05). In the metabolic remodeling phase, the REE formula values calculated by the Third Military Medical University were closest to REE measured values, with significantly lower APE of the REE formula values calculated by the Third Military Medical University formula than those calculated by Milner formula, Hangang formula, and Carlson formula (with t values of 5.12, 2.45, and 6.26, respectively, with all P values <0.05). No significant key factors affected the accuracy of the Peng Xi team's linear formula in the acute inhibition phase ( P>0.05). In the hypermetabolic phase, total burn area was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.00, with 95% confidence interval of 1.00-1.10, P<0.05). In the metabolic balance phase, post-injury days was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.30, with 95% confidence interval of 1.10-1.40, P<0.05). In the metabolic remodeling phase, no significant key factors affected the accuracy of the Third Military Medical University formula ( P>0.05). Conclusions:When calculating REE values in patients with severe burns, it is recommended to use the Peng Xi team's linear formula during the acute inhibition phase, the Hangang formula during the hypermetabolic and metabolic balance phases, and the Third Military Medical University formula during the metabolic remodeling phase. Additionally, it is crucial to ensure the accuracy of key factors affecting the optimal calculation formula in the hypermetabolic and metabolic balance phases.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.