Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective:To evaluate the value of preoperative vascular ultrasound parameters in predicting the postoperative lower extremity deep venous thrombosis (DVT) in patients with gynecological malignant tumors.Methods:Ninety-nine patients with gynecological malignant tumors, aged>18 yr, with body mass index<30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were selected. Vascular ultrasound examination was performed before surgery. The flow velocity and diameter of common femoral vein (CFV), deep femoral vein (DFV), popliteal vein (POV), and intermuscular vein (IMV) were recorded. Ultrasound examination of lower limb veins (including anterior tibial vein, posterior tibial vein, IMV, CFV, DFV, POV) were conducted at 1-8 days after surgery to determine whether a DVT occurred. The receiver operating charcateristic curve was used to evaluate the accuracy of each indicator in predicting the lower extremity DVT, and the cut-off value was determined based on the maximum principle of Jorden index. Results:The incidence of lower extremity DVT was 13.1%. The area under the curve (95% confidence interval) of the preoperative CFV flow velocity and diameter, DFV flow velocity and diameter, POV flow velocity and diameter, IMV flow velocity and diameter in predicting the lower extremity DVT were 0.769 (0.616-0.923) and 0.800 (0.644-0.950), 0.797 (0.641-0.954) and 0.771 (0.596-0.945), 0.806 (0.645-0.968) and 0.754 (0.606-0.903), 0.764 (0.615-0.914) and 0.818 (0.645-0.990), respectively ( P<0.05), and the predicted cut-off values were 27.13 cm/s and 11.93 mm, 19.31 cm/s and 10.15 mm, 16.04 cm/s and 8.79 mm, 14.39 cm/s and 8.68 mm, respectively, and the sensitivity and specificity were 90.0%, 71.4% and 90.0%, 74.3%; 90.0%, 74.3% and 90.0%, 68.6%; 90.0%, 82.9% and 90.0%, 72.9%; 90.0%, 70.0% and 80.0%, 87.1%, respectively. Conclusions:Preoperative vascular vascular ultrasound parameters can accurately predict the occurrence of postoperative lower extremity DVT in patients with gynecological malignant tumors.

Objective: To elucidate the biological basis of the heart qi deficiency (HQD) pattern, an in-depth understanding of which is essential for improving clinical herbal therapy. Methods: We predicted and characterized HQD pattern genes using the new strategy, TCM-HIN2Vec, which involves heterogeneous network embedding and transcriptomic experiments. First, a heterogeneous network of traditional Chinese medicine (TCM) patterns was constructed using public databases. Next, we predicted HQD pattern genes using a heterogeneous network-embedding algorithm. We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq. Finally, we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis. Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism, signal transduction pathways, and immune processes. Moreover, we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern. Furthermore, herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD. Conclusion Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes, but also deciphering the basis of HQD pattern. Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns, leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Micro-computed tomography(Micro-CT)is a non-invasive technology that is widely used in animal experiments to assist in the detection of bone,lung,oral,metabolic,middle and inner ear diseases,as well as tumors,and in other animal disease models.The technique can provide diverse scientific and reliable imaging data for animal experiments and has accordingly become an indispensable experimental method in animal experiments.In this review,we introduce the imaging principles of Micro-CT,review its application in the study of animal disease models,summarize the limitations of Micro-CT technology,and consider its future prospects.

Objective:To search and evaluate the literatures on the application of mechanical insufflation-exsufflation technique (MI-E) in patients with invasive mechanical ventilation in China and abroad, and to summarize the best evidence to provide evidence-based basis for clinical practice.Methods:The literatures related to the use of MI-E technique in invasive mechanical ventilation patients were searched from the establishment of the database to April 1, 2022 in BMJ Best Practice, UpToDate Clinical Advisor, Scottish Intercollegiate Guidelines Network (SIGN), Guidelines International Network (GIN), National Institute for Health and Care Excellence (NICE), National Guideline Clearinghouse (NGC), Registered Nurses' Association of Ontario (RNAO), medlive, Cochrane Library, Joana Briggs Instiute, Web of Science, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database, and Website of American Association for Respiratory Care, including guideline, expert consensus, clinical decision, evidence summary, systematic review and randomized controlled trial. The JBI Center for Evidence-Based Health Care Expert Consensus Evaluation Criteria (2016) was used to evaluate the quality of the included systematic reviews; the JBI Center for Evidence-Based Health Care Evaluation Criteria for Randomized Controlled Trials was used to evaluate the quality of the included randomized controlled trial. Two researchers independently evaluated the quality of literature, and extracted and summarized the evidence based on professional judgment.Results:A total of 7 literatures were enrolled, including 3 systematic reviews and 4 randomized controlled trials. After quality evaluation, 7 articles were all enrolled. Thirteen best evidences were formed from four aspects of indications, contraindications, parameter settings, and attention.Conclusions:The study summarizes the best evidence for the application of MI-E technique in invasive mechanical ventilation patients. It is recommended that medical staff undergo professional training, combined with their professional judgment as well as the patient's clinical specific conditions and willingness, and accurately apply MI-E technology to invasive mechanical ventilation patients.

Three-dimensional (3D) cell culture model is a system that co-culture carriers with 3D structural materials and different types of cells in vitro to simulate the microenvironment in vivo. This novel cell culture model has been proved to be close to the natural system in vivo. In the process of cell attachment, migration, mitosis and apoptosis, it could produce biological reactions different from that of monolayer cell culture. Therefore, it can be used as an ideal model to evaluate the dynamic pharmacological effects of active substances and the metastasis process of cancer cells. This paper compared and analyzed the different characteristics of cell growth and development under two-dimensional (2D) and 3D model culture and introduced the establishment method of 3D cell model. The application progress of 3D cell culture technology in tumor model and intestinal absorption model was summarized. Finally, the application prospect of 3D cell model in the evaluation and screening of active substance was revealed. This review is expected to provide reference for the development and application of new 3D cell culture models.
Cell Culture Techniques, Three Dimensional ; Cell Culture Techniques ; Apoptosis ; Cell Proliferation ; Technology

ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group， model group， and modified Si Junzitang group （12.89 g·kg^-1）. The model group and the modified Si Junzitang group underwent thoracic aortic constriction （TAC）， while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization， microscopic biology， and formula identification were conducted to collect general signs， body weight， open-field behavior， grip strength， mitochondrial ultrastructure， and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC， compared with the sham operation group， the model group showed a significant decrease in left ventricular ejection fraction （LVEF） （P<0.01）， and modified Si Junzitang improved LVEF in mice （P<0.05）. Hematoxylin-eosin （HE） staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group， which was significantly improved by modified Si Junzitang. After 6-8 weeks， compared with the sham operation group and the modified Si Junzitang group， the model group exhibited significant hair loss， hair yellowing， decreased activity， and depression. Moreover， compared with the sham operation group， the model group had a significantly lower increase in body weight （P<0.05）， while the modified Si Junzitang group showed a significant increase in body weight （P<0.05） compared with the model group. After 6-8 weeks， compared with the sham operation group， the model group showed a significant decrease in open-field distance and speed （P<0.05）， while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8^th week （P<0.05）. After 6-8 weeks， compared with the sham operation group， the model group exhibited a significant decrease in maximum grip strength （P<0.05）， while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC （P<0.05）. Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix， mitochondrial swelling， increased volume， matrix dissolution， ridge loss， and vacuolization in the model group， while modified Si Junzitang improved mitochondrial swelling， ridge fracture， and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 （DRP1） in the gastrocnemius muscle of the model group significantly increased （P<0.01）， and the expression of mitochondrial fusion hormone 1 （MFN1） significantly decreased （P<0.05） as compared with those in the sham operation group. Furthermore， compared with the model group， the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 （P<0.05） and a significant increase in MFN1 expression （P<0.01）. ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC， accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle， which were significantly improved by modified Si Junzitang.