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Chaihu and Longgu Muli Decoction has demonstrated significant efficacy in the treatment of tachyarrhythmia accompanied by anxiety and depression. However, there is a lack of standardized guidelines for its clinical application. In this study, the Chaihu and Longgu Muli Decoction was investigated through extensive research on ancient and modern literature, as well as a collection of clinical medical records. The basic information, medication details, and diagnostic information from medical records, personal experience literature, and clinical cases in the treatment of tachyarrhythmia accompanied by anxiety were extracted and analyzed to preliminarily identify the prescription characteristics and syndrome patterns. Subsequently, the Delphi method was employed to construct an item pool based on the data obtained in the first step. An expert questionnaire was prepared to collect scores and revision opinions from experts regarding these items. After statistical analysis and group discussions, a second round of questionnaires was formed by screening out certain items. This process was repeated until a final item set for the treatment of tachyarrhythmia accompanied by anxiety with Chaihu and Longgu Muli Decoction was determined. These findings provided guidance for clinical prescription practices. By extracting 71 syndromes and signs, as well as 33 tongue and pulse characteristics, the main syndrome features included palpitations, chest tightness, irritability, etc., which were basically consistent with the ancient syndromes. Through frequency analysis and group discussions, 71 items were screened out. After screening, modification, and primary and secondary division, 11 main diagnostic items and 10 secondary diagnostic items were determined. On this basis, the research team believes that Chaihu and Longgu Muli Decoction is mainly indicated for the following syndromes in the treatment of tachyarrhythmia accompanied by anxiety(palpitations, poor sleep, bitter taste, dry mouth, irritability/easily angered/anxiety/fearfulness/easily startled, red tongue with greasy yellow coating, rapid pulse, high work/life pressure, tachyarrhythmia on electrocardiogram/Holter monitor, and positive results on anxiety scale). Secondary syndromes include chest tightness, shortness of breath, feeling heavy and weak in the body, sweating, poor appetite, constipation, greasy white tongue coating, wiry pulse, slippery pulse, or knotted and intermittent pulse.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Delphi Technique ; Anxiety/complications* ; Tachycardia/psychology* ; Female ; Male ; Middle Aged ; Adult ; Aged

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective To investigate the effects of Caenorhabditis elegans(C.elegans)endogenous U6 promoters on dpy-10 gene editing efficiency.Methods We screened endogenous U6 small nuclear RNA(snRNA)genes of C.elegans from the WormBase database and constructed 14 editing plasmids targeting dpy-10 by replacing the U6r07e5.16 promoter in the pSX524 plasmid(Peft-3::cas9::tbb-2 terminator::U6 r07e5.16::dpy-10 sgRNA)through molecular cloning.Gene editing was performed in wild-type C.elegans using a standardized microinjection protocol.Gene editing efficiency and the high-efficiency gene editing index were quantified based on the screening of dpy-10 mutant phenotypes in the F1 progeny.Results A total of 15 U6 snRNA genes(r07e5.16,f35c11.9,t20d3.13,k09b11.15,k09b11.16,w05b2.8,c28a5.7,f54c8.9,k09b11.11,k09b11.12,k09b11.14,t20d3.12,f54c8.8,f54c8.10,and k09b11.13)were identified from the WormBase database.Based on the editing efficiency and high-efficiency gene editing index,the activity of these promoters was evaluated,and 4 U6 promoters(w05b2.8,c28a5.7,f54c8.9,and k09b11.11)were found to have significantly enhanced gene editing success rates,outperforming other promoters,including U6r07e5.16 and U6k09b11.12,which are commonly used in the C.elegans research community.Notably,the gRNAF+E scaffold did not show superior editing efficiency over the gRNA scaffold when paired with the optimal U6w05b2.8 promoter.Conclusion In this study,U6 promoters that significantly improve gene editing efficiency in C.elegans are identified and the critical role of promoter optimization in CRISPR-Cas9 systems is highlighted.These findings provide a valuable foundation for improving genome editing strategies and offer new ideas for optimizing the CRISPR technology applied in nematode research.

Objective To optimize the real-time quantitative polymerase chain reaction(RT-qPCR)data analysis process through mathematical principles by replacing the biased 2-??CT method with a more rigorous 2-CT method,thereby improving the accuracy of gene expression quantification analysis.Methods Essentially,the CT value serves as the exponent in a base-2 exponential equation within the logic of comparative CT method.In the traditional 2-??CT method,the arithmetic means of raw CT and ΔCT values are directly calculated and the exponential nature of CT data is overlooked,which may introduce systematic bias to the calculation results.We propose a new method,entitled the 2-CT method,in which all calculations are based on the transformation of CT values into 2-CT.This includes computing the relative initial expression levels of target and reference genes within each sample,the relative abundance of the target gene,and its fold change across groups.Statistical comparisons are then performed based on fold change values.By strictly adhering to the exponential nature of of CT values,the biases introduced by arithmetic averaging at the CT or ΔCT level are avoided.We applied this method to multiple RT-qPCR datasets to evaluate the differences between the traditional 2-??CT and the proposed 2-CT methods in gene expression quantification,as well as the effect of the differences.Results In the original dataset from LIVAK and SCHMITTGEN,the two methods produced similar results.However,in the cadmium exposure experiment,findings from the 2-??CT method indicated that 8-hour cadmium exposure caused an increase of irg-6 gene expression in Caenorhabditis elegans from 1.314-fold to 7.125-fold(P=0.000 2).In contrast,findings from the 2-CT method showed a fold change from 1.0 to 4.124(P=0.001 5),a 70%difference between the two methods.Conclusion The2-CT method provides a mathematically more rigorous approach that more accurately reflects gene expression changes,particularly in experiments with high CT variability.It offers a more reliable computational paradigm for quantitative gene expression analysis.

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P＜0.01,P＜0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Objective To explore the effects and related mechanisms of astragaloside Ⅳ on depression-like behavior in rats with post-stroke depression(PSD)induced by chronic unpredictable mild stress(CUMS).Methods Fifty-four healthy male Sprague Dawley rats were randomly divided into blank group,sham surgery group,physiological saline group,astragalosideⅣ group,fluoxetine group,and combination therapy group,with 9 rats in each group.Rats in the blank group were raised normally without any treatment.After anesthesia,rats in the sham surgery group were exposed to the common carotid artery through a longitudinal incision about 2 cm along the right neck.The incision was not processed and sutured directly,and the rest were the same as those in the blank group.Rats in the remaining four groups were first used to prepare rat stroke models according to the suture method,and then CUMS induction was performed to prepare PSD models.After successful modeling,the rats in the physiological saline group were given physiological saline(5 mL·kg-1)daily by gavage,the rats in the astragaloside Ⅳ group were given astragaloside Ⅳ suspension(25.0 mg·kg-1)daily by gavage,the rats in the fluoxetine group were given fluoxetine suspension(12.5 mg·kg-1)daily by gavage,and the rats in the combination therapy group were given astragaloside Ⅳ(25.0 mg·kg-1)and fluoxetine(12.5 mg·kg-1)suspensiondaily by gavage.All rats in the four groups were administered once a day for a total of 4 weeks.The rats in the blank group and sham surgery group did not undergo gastric lavage treatment.The body mass was measured once a week,and the sucrose preference test,open field test,and Morris water maze test were also conducted once a week until the end of the experiment.After the administration,the rats were euthanized.The expression levels of adenosine monophosphate-activated protein kinase(AMPK)and brain-derived neurotrophic factor(BDNF)mRNA in the hippocampus of rats in each group were detected by reverse transcription polymerase chain reaction.The relative content of AMPK and BDNF positive cells in the hippocampus of rats in each group was detected by immunohisto-chemical staining.The expression levels of AMPK and BDNF protein in the hippocampus of rats in each group were detected by Western blot.Results After 4 weeks of treatment,there was no statistically significant differences in body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats between the blank group and the sham surgery group(P＞0.05);compared with the blank group and sham surgery group,the body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats in the physiological saline group,astragaloside Ⅳ group,fluoxetine group,and combination therapy group were significantly reduced(P＜0.05);compared with the physiological saline group,the body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats in the astragaloside Ⅳ group,fluoxetine group,and combination therapy group significantly increased(P＜0.05);there was no statistically significant differences in body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequencyof rats among the astragaloside Ⅳ group,fluoxetine group,and combination therapy group(P＞0.05).After 4 weeks of treatment,there was no statistically significant differences in the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats between the blank group and the sham surgery group(P＞0.05);compared with the blank group and sham surgery group,the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats in the physiological saline group,astragaloside Ⅳ group,fluoxetine group,and combination therapy group significantly decreased(P＜0.05);compared with the physiological saline group,the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats in the astragaloside Ⅳ group,fluoxetine group,and combination therapy group increased(P＜0.05);there was no statistically significant differences in the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats among the astragaloside Ⅳ group,fluoxetine group,and combination therapy group(P＞0.05).Conclusion Astragaloside Ⅳ can improve depression-like behavior in CUMS-induced PSD rats,and its mechanism may be related to increasing the expression of AMPK and BDNF in the hippocampus.

Objective To propose a multi-cascade deep learning processor-based surgical instrument detection and pose estimation algorithm to facilitate the robotic scurb nurse to recognize and delivery surgical instruments.Methods The proposed multi-cascade deep leaning processor-based CYSP algorithm was hibernated with several functional modules such as YOLOX with coordinate attention block(CA-YOLOX),segment anything model(SAM)and principal component analysis(PCA).Firstly,CA-YOLOX was applied to identifying the types of the surgical instruments and completing the coarse positioning of x and y coordinates;secondly,the SAM segmenter was used to clarify the positions of the instruments in the RGB image,and the depth information and internal parameters of the camera were introduced to obtain the point cloud of the surgical instruments;finally,the center of mass,principal direction and normal direction of the surgical instrument point cloud were determined through the PCA algorithm,with which the rotation and translation(RT)matrix between the target coordinate system(surgical instrument center of mass coordinate system)and the base coordinate system of the robotic arm was solved,and the matrix was converted into a quaternion and then transmitted to the robotic arm control unit so as to drive the robotic arm to arrive at the corresponding position and pick up the instrument to complete the instrument delivery task.Migration training was accomplished on a self-constructed surgical instrument image dataset and the effectiveness of the proposed algorithm was evaluated,and instrument delivery experiments were performed on a seven-degree-of-freedom robotic arm and the success rate of the algorithm was assessed.Results The multi-cascade deep leaning processor-based CYSP algorithm had a recognition accuracy of 98.52％on the surgical instrument dataset,a success rate of 94％for the in-strument delivery experiment and average time for recognition of 0.28 s.Conclusion The multi-cascade deep leaning proces-sor-based CYSP algorithm with high reliability and practicability behaves well in facilitating the robotic scurb nurse to recog-nize and deliver surgical instruments.[Chinese Medical Equipment Journal,2024,45(6):1-8]