Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

Background Under the background of global warming, research on association between ambient temperature and risk of injury is needed. Objective To examine the effect of temperature on injury in Bao'an district, Shenzhen and identify the sensitive population, thereby providing a scientific basis for formulating prevention and control strategies and measures of injury. Methods The injury reports from the Injury Surveillance System and the meteorological data of Bao'an District between 2018 to 2022 were collected. The meteorological data were sourced from the fifth generation of the European Centre for Medium-Range Weather Forecasts (ECMWF) land reanalysis data. Based on time-stratified case-crossover design, conditional logistic regression combined with distributed lag nonlinear model was used to evaluate the exposure-response association between ambient temperature and injury. The stratified analyses were further conducted by gender, age, and causes of injury. Results A total of 156205 injury cases were collected from the injury surveillance sentinel hospitals in Bao'an District of Shenzhen from 2018 to 2022, and the median of daily average temperature during the same period was 20.0 ℃. The exposure-response curve showed that the risk of injury was positively correlated with temperature. The linearized analysis revealed that each 1°C increase in temperature was associated with a 1.05% (95%CI: 0.68%, 1.42%) rise in injury risk (ER). Notably, the effect was greater in females (ER=1.31%, 95%CI: 0.67%, 1.94%) than males (ER=0.92%, 95%CI: 0.47%, 1.37%). Among age groups, adults ＞60 years faced the highest risk (ER=1.91%, 95%CI: −0.36%, 4.24%). The top three temperature-associated injury risks were sharp instrument injuries (ER=2.19%, 95%CI: 1.16%, 3.22%), animal injuries (ER=1.71%, 95%CI: 0.86%, 2.56%), and blunt injuries (ER=071%, 95%CI: −0.08%, 1.51%). The impact of temperature on unintentional injuries (ER=1.11%, 95%CI: 0.72%, 1.49%) was higher than that on intentional injuries (ER=0.43%, 95%CI: −0.85%, 1.72%). Severe injuries (ER=2.20%, 95%CI: −3.09%, 7.77%) were more affected by temperature than mild injuries (ER=1.00%, 95%CI: 0.58%, 1.43%) and moderate injuries (ER=1.15%, 95%CI: 0.42%, 1.89%). Conclusion The increase in ambient temperature associates with injury occurrence, and the impact of temperature exhibits obvious heterogeneity among different populations, indicating that targeted intervention measures should be taken for different populations and types of injuries.

Guided by the theory of turbid pathogen disturbing clarity， this paper holds that the pathogenesis of otolith disorders involves the failure of clear yang to ascend and the internal generation of phlegm-turbidity as the initiating factors. The clinical manifestations are characterized by the intermingling of phlegm and fluid， as well as the disturbance between turbid and clear substances， while the root lies in spleen-kidney deficiency and depletion of primordial qi. Treatment strategies are formulated according to the different stages of the disease： in the acute phase， therapy focuses on warming and resolving phlegm-fluid retention， using a modified combination of Linggui Zhugan Decoction （苓桂术甘汤） and Zexie Decoction （泽泻汤）； in the residual phase， the approach shifts to tonifying qi and uplifting clear yang， with a modified combination of Shengxian Decoction （升陷汤） and Shengmai Power （生脉散）； in the consolidation phase， therapy aims to tonify the kidney and replenish essence， employing a modified version of Qiju Dihuang Pill （杞菊地黄丸）.

Emergence agitation （EA） is a common complication after general anesthesia， especially in children and adolescents. Remifentanil， as a short-acting μ-receptor agonist， has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network， including regulation of microglial inflammatory pathways， and the modulation of cytokines and chemokines，etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time， reduce the incidence of EA， and further optimize the analgesic effect and recovery quality by combining with other drugs （such as local anesthetics， sedatives， and opioid drugs）. Future research should further explore the mechanism of action of remifentanil， optimize clinical treatment strategies， and conduct large- scale clinical trials to standardize the drug use plan， while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.

ObjectiveTo observe the clinical effect of Jieyu Qingxin formula granules combined with remote interactive cognitive behavioral therapy for insomnia （CBT-I） on chronic insomnia of liver depression and fire-turning type. MethodThis study was a prospective randomized controlled trial. 120 patients with chronic insomnia of liver depression and fire-turning type in Lu'an traditional Chinese medicine Hospital from January 2022 to June 2023 were selected as objects. They were randomly divided into two groups，with 60 cases in each group. The control group received remote interactive CBT-I. The observation group was treated with Jieyu Qingxin formula granules on the basis of the control group. Intervention treatment lasted for four weeks，and observation lasted for six weeks. Comparison of data of each group：clinical efficacy，changes in traditional Chinese medicine （TCM） syndrome score before and after treatment，changes in insomnia severity index （ISI） score，self-rating depression scale （SDS） and self-rating anxiety scale （SAS） score changes，total sleep time，wake time，sleep latency，sleep efficiency， Actigraphy sleep parameter value changes，serum neuron specific enolase （NSE） ，adenosine，dopamine （DA）， 5-hydroxytryptamine （5-HT） level changes，and adverse reactions. ResultThe total effective rate in the observation group （92.45%，49/53） was higher than that in the control group（76.92%，40/52）， and the difference was statistically significant（χ²=4.711 1，P<0.05）. After treatment，TCM syndrome score，ISI score，SAS score， and SDS score were decreased in all groups. The total sleep time was extended，and wake time and sleep latency were shortened. The sleep efficiency was increased，but the NSE and DA levels were decreased. Adenosine and 5-HT levels were increased in all groups（P<0.05）. After treatment，compared with the control group，the observation group had lower TCM syndrome score，ISI score，SAS score， and SDS score，longer total sleep time，higher sleep efficiency，shorter wake time and sleep latency，lower NSE and DA levels， and higher adenosine and 5-HT level （P<0.05）. There was one case of nausea in the observation group and no adverse reaction in the control group during treatment. There was no significant difference between the two groups. ConclusionBy reducing NSE and DA and increasing the levels of 5-HT and adenosine，the anxiety （SAS score） and depression （SDS score） of patients can be improved， so as to improve their sleep and effectively treat chronic insomnia of liver depression and fire-turning type.

Heart failure （HF） is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping， seriously affecting patients' health and quality of life. The pathogenesis of HF is complex， including myocardial contractility decline， myocardial fibrosis， and ventricular remodeling， and it is related to neuroendocrine regulation， inflammation， and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF， moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism， while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine （TCM） with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF， introduces the understanding of autophagy， AMPK/mTOR signaling pathway， and HF based on TCM theories， and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases， provide theoretical support for subsequent experimental studies， and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.

Objective To investigate the risk factors for arrhythmia after robotic cardiac surgery. Methods The data of the patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed. According to whether arrhythmia occurred after operation, the patients were divided into an arrhythmia group and a non-arrhythmia group. Univariate analysis and multivariate logistic analysis were used to screen the risk factors for arrhythmia after robotic cardiac surgery. Results A total of 146 patients were enrolled, including 55 males and 91 females, with an average age of 43.03±13.11 years. There were 23 patients in the arrhythmia group and 123 patients in the non-arrhythmia group. One (0.49%) patient died in the hospital. Univariate analysis suggested that age, body weight, body mass index (BMI), diabetes, New York Heart Association (NYHA) classification, left atrial anteroposterior diameter, left ventricular anteroposterior diameter, right ventricular anteroposterior diameter, total bilirubin, direct bilirubin, uric acid, red blood cell width, operation time, CPB time, aortic cross-clamping time, and operation type were associated with postoperative arrhythmia (P<0.05). Multivariate binary logistic regression analysis suggested that direct bilirubin (OR=1.334, 95%CI 1.003-1.774, P=0.048) and aortic cross-clamping time (OR=1.018, 95%CI 1.005-1.031, P=0.008) were independent risk factors for arrhythmia after robotic cardiac surgery. In the arrhythmia group, postoperative tracheal intubation time (P<0.001), intensive care unit stay (P<0.001) and postoperative hospital stay (P<0.001) were significantly prolonged, and postoperative high-dose blood transfusion events were significantly increased (P=0.002). Conclusion Preoperative direct bilirubin level and aortic cross-clamping time are independent risk factors for arrhythmia after robotic cardiac surgery. Postoperative tracheal intubation time, intensive care unit stay, and postoperative hospital stay are significantly prolonged in patients with postoperative arrhythmia, and postoperative high-dose blood transfusion events are significantly increased.