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 effect of propranolol on femoral fracture healing in mice through regulation of microRNA-92a-3p(miR-92a-3p)and its mechanism.Methods C57BL/6J male mice were randomly divided into sham group(equal amount of 0.9％NaCl),model group(equal amount of 0.9％NaCl),experimental group(50 mg·kg-1 propranolol administration),inhibitor group(mice were injected with 100 mg·kg-1 miR-92a-3p inhibitor via tail vein on the basis of the experimental group).Femur was severed and molded in all mice except sham operation group.X-ray was used to observe bone healing.Quantitative real time polymerase chain reaction was used to detect the expression of miR-92a-3p in femur tissues.The expression level of bone formation and bone metabolism markers was detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression of pathway-related proteins.Results The X-ray scores of femur in sham group,model group and experimental group were 11.20±2.60,4.70±1.50 and 9.60±2.40,respectively;the relative expression levels of miR-92a-3p in sham operation group,model group,experimental group and inhibitor group were 1.00±0.09,0.73±0.06,0.90±0.07 and 0.78±0.06;alkaline phosphatase levels were(35.21±2.63),(43.16±3.29),(67.58±5.37)and(49.62±4.05)U·L-1,respectively;crosslaps levels were(4.57±0.52),(8.41±0.91),(4.26±0.67)and(5.73±0.84)ng·mL-1,respectively;the relative expression levels of brain derived neurotrophic factor were 1.00±0.14,0.58±0.05,0.83±0.09 and 0.71±0.06,respectively;the relative expression levels of phospho-tyrosine kinase receptor B were 1.00±0.12,0.62±0.05,0.89±0.08 and 0.76±0.07,respectively;the relative expression levels of phospho-extracellular regulated protein kinases were 1.00±0.11,0.54±0.04,0.78±0.07 and 0.65±0.05,respectively.The above indexes in the model group were compared with those in the sham group,those in the experimental group were compared with those in the model group,and those in the inhibitor group were compared with those in the experimental group,and the differences were statistically significant(P＜0.05,P＜0.001).Conclusion Propranolol can promote femoral fracture healing in mice,which may be achieved by up-regulating miR-92a-3p activation of brain derived neurotrophic factor/tyrosine kinase receptor B/extracellular regulated protein kinases signaling pathway.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective To study the traditional Chinese medicine(TCM)constitution characteristics of overweight/obese patients in Shanghai region and to investigate the correlation of TCM constitution with body composition.Methods Relevant data were collected from the patients with complete information of TCM constitution and human body composition analysis who visited the specialized outpatient clinic of acup-moxibustion catgut embedding therapy in the Department of Endocrinology,Shanghai Tenth People's Hospital from August 2020 to December 2022.The patients were divided into a normal body mass group(BMI＜24 kg/m2),an overweight group(24 kg/m2≤BMI＜28 kg/m2)and obesity group(BMI≥28 kg/m2),and then the distribution of TCM constitution types in the three groups of patients were analyzed.After that,the correlation between TCM constitution and body composition were explored with multiple regression analysis.Results(1)A total of 315 patients were included,of which 43 patients had normal body mass,85 patients were overweight and 187 patients were obese.(2)The TCM constitution types in descending order of the composition ratio in the normal body mass group and in the overweight group were spleen deficiency constitution,liver stagnation constitution,damp-heat constitution,yang deficiency constitution,and yin deficiency constitution,in the obese group were spleen deficiency constitution,yang deficiency constitution,damp-heat constitution,liver stagnation constitution,and yin deficiency constitution,and in the overweight/obese group were spleen deficiency constitution,damp-heat constitution,yang deficiency constitution,liver stagnation constitution,and yin deficiency constitution.No statistically significant differences of the distribution of TCM constitution types were shown between normal body bass population and overweight/obese population(P＞0.05).In both normal body mass population and overweight/obese population,the single body constitution type was common,and biased constitution was rare,and there was no statistically significant difference when comparing between the two groups(P＞0.05).(3)The results of multiple regression analysis showed that the basal metabolism of all patients was positively correlated with yang deficiency constitution and was negatively correlated with damp-heat constitution,and the differences were statistically significant(P＜0.01).It is indicated that if the score of yang deficiency constitution rose by one point,the basal metabolism would increase by 0.54 kcal,and if the score of damp-heat constitution decreased by one point,the basal metabolism would decrease by 1.005 kcal.Conclusion In Shanghai region,obesity may be the main indication of the variation of the body constitution.In addition to spleen deficiency constitution,the proportions of yang deficiency constitution,damp-heat constitution and liver stagnation constitution are also higher in obese patients.In terms of the correlation between TCM constitution and body composition,basal metabolism is positively correlated with yang deficiency constitution and is negatively correlated with damp-heat constitution.Therefore,for the patients with yang deficiency constitution and damp-heat constitution,the influence of the basal metabolism level on the development of the disease should be taken into account.

Objective To discuss the feasibility and safety of simultaneous bilateral adrenal vein sampling(AVS)using two 4F-MPA1 catheters via right elbow vein access.Methods A total of 51 consecutive patients with primary aldosteronism,who received simultaneous bilateral AVS using two 4F-MPA1 catheters(one of the two catheters was shaped into pig tail figure)via right elbow vein access at Xiangyang Municipal Central Hospital between October 2021 and October 2022,were enrolled in this study.The used catheter,the success rate of simultaneous bilateral AVS,and the incidence of complications rate were calculated.Results The 4F-MPA1 catheter was used for all of the right AVS,while a specially shaped 4F-MPA1 catheter was used for the main trunk vein AVS of the left adrenal gland and the central vein AVS of the left adrenal gland.The success rate of simultaneous bilateral AVS was 92.2%(47/51).Adrenal hematoma occurred in one patient(1.96%).Conclusion The technique of simultaneous bilateral AVS using two 4F-MPA1 catheters via right elbow vein access is simple to operate,less traumatic,and clinically safe and feasible.However,due to the small sample used in this study,the clinical value of this technique still needs further investigation and verification.

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.