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Biejiajian Wan， a classical formula for liver diseases， originated from Synopsis of the Golden Chamber. It has been applied in clinical settings for more than 2 000 years. According to modern pharmacological studies， it has anti-tumor， anti-fibrosis， and immunity-enhancing effects and thus is widely used for the treatment of liver fibrosis， hepatitis， liver injury， and other diseases. In recent years， accumulating evidence has proven the efficacy of this formula in the treatment of malignant tumors， especially liver cancer. This paper summarizes relevant papers in the last 20 years and summed up the anti-liver cancer mechanisms of Biejiajian Wan as regulating biological behaviors of liver cancer cells， anti-precancerosis， inhibiting tumor angiogenesis， modulating signaling pathways， suppressing activity of relevant enzymes， and regulating immunity. Moreover， this prescription can inhibit the proliferation， invasion， and metastasis of liver cancer cells， promote apoptosis of cells， suppress tumor angiogenesis， and boost immunity. In addition， it regulates Wnt/β-catenin， interleukin-6/signal transducer and activator of transcription 3 （IL-6/STAT3）， NOD-like receptor protein 3 （NLRP3）， Janus kinase-signal transducers and activators of transcription （JAK-STAT）， Delta-like ligand 4-Notch （DLL4-Notch）， nuclear factor-κB （NF-κB）， Rho-associated kinase （Rho/ROCK）， transforming growth factor-β/Smad （TGF-β/Smad）， phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3β （PI3K/Akt/GSK-3β）， and other signaling pathways. Thus， Biejiajian Wan is confirmed to have anti-liver cancer effect based on the molecular mechanisms. According to the summary of Biejiajian Wan in anti-liver cancer treatment， Biejiajian Wan alone or in combination with other drugs can significantly alleviate the symptoms， reduce adverse reactions， prolong the survival time with definite efficacy. Thus， it is safe with no adverse reactions in long-term use， which should be further promoted in clinical application. This paper analyzed Biejiajian Wan in the treatment of liver cancer based on the molecular mechanisms and clinical studies， summarized the limitations in current research， and put forward suggestions， which can lay a basis for the future in-depth research on and clinical application of Biejiajian Wan and development of anti-tumor drugs.
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ObjectiveTo explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia （FD） based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 2 （ROCK2）/Myosin phosphatase target Subunit 1 （MYPT1） pathway. MethodSixty male SD suckling rats in SPF grades were randomly divided into blank group （n=10） and model group （n=50）. The comprehensive modeling method （gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety） was used to replicate the rat model of FD. After successful replication of the model， the rats in the model group were randomly divided into model group， mosapride group， and high， middle， and low-dose Xiangsha Liujunzi Tang groups， with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg-1·d-1 normal saline， those in the mosapride group were given 1.35 mg·kg-1·d-1 mosapride， and those in the high， middle， and low-dose Xiangsha Liujunzi Tang groups were given 12， 6， and 3 g·kg-1·d-1 Xiangsha Liujunzi Tang， respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration， and the 3-hour food intake and body mass of rats were measured. After intervention， the intestinal propulsion rate of rats was measured， and the pathological changes in the gastric tissue were observed by hematoxylin-eosin （HE） staining. The content of choline acetyl transferase （ChAT） and vasoactive intestinal peptide （VIP） in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay （ELISA）， the distribution of adenosine triphosphate （ATP） enzyme in gastric antrum smooth muscle was observed by frozen section staining， and the protein expression levels of RhoA， ROCK2， and phosphorylated-myosin phosphatase target subunit 1 （p-MYPT1） in the gastric tissue were detected by Western blot. ResultCompared with the blank group， the model group had withered hair， lazy movement， slow action， poor general living condition， lower 3-hour food intake， body mass， and lower intestinal propulsion rate （P<0.05）， whereas no obvious abnormality in gastric histopathology. In the model group， the content of ChAT in the medulla oblongata and gastric tissue decreased， the content of VIP in gastric tissue increased， the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue decreased significantly （P<0.05）. As compared with the model group， the general living condition of rats in each intervention group was significantly improved， and the 3-hour food intake， body mass， and intestinal propulsion rate were significantly increased （P<0.05）. There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly， the content of VIP in the gastric tissue decreased， the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue increased significantly （P<0.05）. The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent. ConclusionXiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD， and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.
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ObjectiveTo explore the weights and comprehensive indices of each field of intrinsic capacity of old adults, and the correlation between intrinsic capacity and activities of daily living (ADL). MethodsThe data of 5 506 cases aged more than 60 years in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were used to collect the assessment of intrinsic capacity and the measurement of ADL. The assessment of intrinsic capacity included cognition, motor, vitality, sensory and psychology; while the ADL scale included six indicators, namely dressing, bathing, eating, getting in or out of bed, going to the toilet, and controlling urine and feces. ResultsA total of 1 343 cases were limited in ADL (24.4%). Women, lower education level, older age, the widowed, greater number of chronic diseases, and poorer self-rated health were the factors more likely to be limited in ADL. Principal component analysis showed that the largest weight value was in psychological domain, followed by the cognitive domain, and the lowest weight value was in the motor domain. After controlling for the effects of age, gender, living environment, economic income, education level, marriage, smoking and drinking, number of chronic diseases, and self-rated health, the Logistic regression analysis showed that low exercise capacity (OR = 0.581, 95%CI 0.501 to 0.674), depression (OR = 0.426, 95%CI 0.368 to 0.493), audile and visual impairment (OR = 0.813, 95%CI 0.699 to 0.947; OR = 0.684, 95%CI 0.578 to 0.809), overweight (OR = 1.203, 95%CI 1.014 to 1.428) and obesity (OR = 1.584, 95%CI 1.312 to 1.912) were independent risk factors for ADL limitation in older adults. ConclusionDecrease of intrinsic capacity is a predictor for ADL limitation in older adults.
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Background In the process of radiotherapy, when radiation kills tumor cells, it inevitably damages normal tissue cells. Objective To investigate the role of Toll-like receptor 4 (TLR4)/nuclear factor−kappa B (NF-κB) signaling pathway in the improvement of cognitive impairment induced by ionizing radiation by hydrogen-rich water before and after whole brain irradiation in rats. Methods Fifteen male SD rats were randomly divided into three groups: control group, irradiated group (IR group), and hydrogen-rich water intervention group (IR+HRW group), with 5 rats in each group. The control group was not irradiated, but was given purified water (20 mL·kg−1) by gavage every day, while the IR group and the IR+HRW group were irradiated with a single dose of 20 Gy. Three days before, 10 min before, and 30 days after irradiation, purified water/hydrogen-rich water (20 mL·kg−1) was given by continuous gavage every day. The general condition of the rats was observed every day, and the body weight were measured on the 7th, 14th, 21st, and 30th days after irradiation. On the 30th day after irradiation, the learning and memory ability of the rats was tested by Morris water maze; the pathological changes of hippocampus were detected by hematoxylin-eosin (HE) staining after sacrificing the rats; the contents of glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), and hydroxyl radicals in brain tissues were detected by enzyme linked immunosorbent assay (ELISA); the mRNA and protein expression levels of TLR4, NF-κB, NOD-like receptor pyrin domain 3 (NLRP3), and cysteinyl aspartate specific proteinase 1 (Caspase 1) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting in the hippocampus of rats. Results After irradiation, the rats in the IR group showed symptoms such as head hair removal and salivation, while the symptoms of the rats in the IR+HRW group were milder. No animal died in the control and the IR+HRW groups, while one rat died in the IR group. From day 14 to day 30 after irradiation, the body weight of the rats in the IR+HRW group tended to be higher than that in the IR group, but the difference was not statistically significant (P>0.05). The Morris water maze results showed that the escape latency of the IR+HRW group was shortened compared with that of IR group from day 1 to day 5 except day 3, but the difference was not statistically significant (P>0.05). For the rats in the IR+HRW group, it took less time to reach the original location of the platform after removing the platform on day 6 and the number of crossing the platform and the residence time in the original platform quadrant increased (P<0.05). The HE staining showed that the number of hippocampal cells in the IR+HRW group was slightly reduced and arranged neatly, without obvious nuclear hyperchromatic and pyknotic phenomenon. The ELISA results showed that the MDA and hydroxyl radical levels were decreased in the IR+HRW group compared with the IR group (P<0.05), the GSH content was increased, and the IL-1β concentration was decreased, but the differences were not statistically significant (P>0.05). The results of qRT-PCR showed that the mRNA expression levels of TLR4 and Caspase 1 in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the mRNA expression levels of NF-κB and NLRP3 were also decreased, but the differences were not statistically significant (P>0.05). The results of Western blotting showed that the expression levels of TLR4 and Caspase 1 protein in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the expression levels of NF-κB p65 and NLRP3 protein were also decreased, but the differences were not statistically significant (P>0.05). Conclusion Hydrogen-rich water can improve cognitive impairment induced by ionizing radiation in rats, and its mechanism may be related to regulating TLR4/NF-κB signaling pathway, inhibiting inflammatory factors, and attenuating oxidative stress.
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Background At present, radiation therapy is widely used in clinical treatment of tumors. However, while radiation therapy damages tumor cells, it also injures surrounding normal tissues. Studies have shown that hydrogen is a potential radiation-protective agent. Objective To investigate the neuroprotective mechanisms of hydrogen-rich water activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/cysteinyl aspartate specificproteinase-9 (Caspase-9) signaling pathway in acute radiation-induced brain injury. Methods Forty male SD rats were randomly divided into four groups: control group, irradiation only group (IR), high-dose hydrogen-rich water intervention group (IR+HHRW), and low-dose hydrogen-rich water intervention group (IR+LHRW), 10 rats in each group. Except for the control group, animals in each group received a single 20 Gy whole brain irradiation. Animals in all groups were gavaged once a day from 3 d before irradiation to 7 d after irradiation, pure water (20 mL·kg−1) was given to the control and the IR groups, and hydrogen-rich water (20 mL·kg−1, 10 mL·kg−1) was given to the IR+HHRW and the IR+LHRW groups. After 7 d of intervention, 5 rats in each group were selected for the Morris water maze experiment for behavioral evaluation. Autopsies were conducted after anesthesia for the remaining animals and blood samples were collected for hematological analysis. Rat brains were harvested for TUNEL staining to observe neuronal apoptosis. HE staining was performed to observe histopathological changes, enzyme-linked immunosorbent assay was adopted to detect oxidative stress-related indicators, and real-time PCR and Western blotting were used to measure the expressions of PI3K/AKT/Caspase-9 pathway-related genes and proteins. Results The body weight of rats receiving irradiation decreased after 7 d of irradiation compared with the control group (P<0.05), and the symptoms such as arched back and malaise occurred to varying degrees, and the symptoms of rats in the IR+HHRW group were significantly milder than those in the IR group. The behavioral test results showed that the escape latency of rats in the IR+HHRW group or the IR+LHRW group was shorter than that in the IR group from day 2 to day 5 (P<0.05), and it took less time for rats in the IR+HHRW group to reach the original position after removing the platform on day 6 (P<0.05). The hematological test results showed that red blood cell (RBC) count, hemoglobin (HGB) level, and white blood cell (WBC) count were significantly decreased in the IR group (P<0.05), and the changes in the IR+HHRW group were improved (P<0.05). The HE staining results showed that the number of abnormal nerve cells, broken and dissolved nuclei, and the degree of damage in the IR+HHRW group were significantly reduced than those in the IR group. The results of oxidative stress evaluation showed that the ability of the IR group to inhibit free radicals decreased, the level of malondialdehyde (MDA) increased (P<0.01); the MDA level decreased after LHRW intervention (P<0.05); the SOD activity was elevated after HHRW intervention (P<0.05). The TUNEL staining results showed that the apoptosis signals in the IR+HHRW group were sparser than those in the IR group (P<0.05). The real-time PCR results showed that compared with the IR group, the mRNA expression levels of PI3K and AKT in the IR+HHRW group and the IR+LHRW group increased (P<0.05), while the mRNA expression levels of Cytc and Caspase-9 decreased (P<0.05). The Western blotting results showed that compared with the IR group, the phospho-AKT (pAKT) protein expression level in the IR+HHRW group increased significantly (P<0.05), while the expression of Caspase-9 and Cytc proteins decreased significantly (P<0.05). Conclusion Hydrogen-rich water can significantly reduce inflammation and oxidative stress caused by acute irradiation-induced brain injury, and decrease neuronal apoptosis. The mechanism may be related to the PI3K/AKT/Caspase-9 signaling pathway.
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Objective:To understand the level of thirst distress in heart failure and analyze its influencing factors, in order to provide a theoretical basis for implementing the intervention measures to alleviate patients′ thirst distress.Methods:A total of 187 patients with heart failure who met the inclusion criteria from the First Affiliated Hospital and the Second Affiliated Hospital of Dalian Medical University from November 2019 to October 2020 were selected as the research objects. The General Information Questionnaire, Thirst Distress Scale-Heart Failure, Generalized Anxiety Disorder 7-item Scale, Patient Health Questionaire-9 and Brief Illness Perception Questionnaire were used to investigate heart failure patients. Multiple linear regression was used to explore the influencing factors of heart failure patients′ thirst distress.Results:The score of thirst distress in heart failure patients was (23.95 ± 4.21), multiple stepwise linear regression analysis showed that heart function grade, diuretic usage, anxiety, depression and disease perception were the influencing factors of thirst distress in patients with heart failure, which explained 41.9% of the thirst distress in heart failure patients.Conclusions:The thirst distress of heart failure patients is in the middle level, and its thirst distress is affected by many factors, clinical medical staff should pay attention to the severity of thirst distress in patients with heart failure, actively develop different intervention measures to reduce patients′ thirst sensation, and explore effective schemes to alleviate thirst distress in patients with heart failure.
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Objective:To investigate the effect of mind mapping on the discharge readiness of patients undergoing first coronary stent implantation, so as to provide basis for seeking effective discharge guidance in clinical practice.Methods:One hundred patients who were hospitalized in the Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University from December 2019 to August 2020 and who underwent coronary stent implantation for the first time were selected as the study objects. They were divided into the control group and the experimental group with 50 cases in each group by the random number table method. The control group was given routine discharge guidance, and the experimental group was given discharge guidance using mind mapping. Readiness for Hospital Discharge Scale and Quality of Discharge Teaching Scale were used to compare the differences of discharge readiness and discharge guidance quality between the two groups after intervention.Results:The personal status, adaptability, predictive support and the total score of discharge readiness in the experimental group were (25.18 ± 3.79), (45.24 ± 3.63), (36.62 ± 3.63), (107.04 ± 8.92) points, which were all higher than those in the control group (23.34 ± 3.04), (41.68 ± 3.62), (35.14 ± 2.14), (100.16 ± 7.36) points, with statistically significant differences ( t values were -4.91--2.48, all P<0.05). The actual acquired content, guiding skills and results, total scores of discharge guidance quality of patients in the experimental group were (56.66 ± 6.06), (94.46 ± 4.33), (151.12 ± 8.26) points, which were all higher than those in the control group (45.38 ± 9.19), (89.44 ± 10.87), (134.82 ± 14.31) points, with statistically significant differences ( t values were -7.25, -3.03, -6.97, all P<0.05). Conclusions:Mind mapping can effectively improve the discharge preparation degree and discharge guidance quality of patients undergoing coronary stent implantation for the first time, and it is a simple and practical discharge guidance tool.
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Objective To investigate the protective effect of hydrogen-rich water on rat cognitive dysfunction induced by ionizing radiation.Methods A total of 20 SD rats were randomly divided into four groups with the ramdom number table method: control group(C),hydrogen-rich water group(HRW),irradiation group(IR)and hydrogen-rich water intervention group(HRW+IR),with 5 rats in each group.The spatial memory ability of rats was tested by a morris water maze.The expression of apoptosis-related genes was detected by real-time fluorescence quantitative PCR.The changes of glutathione(GSH),8-hydroxydeoxy guanosine(8-OHdG)and malondialdehyde(MDA)and SOD were also measured.Results The escape latency(F＝6.003,P＜0.05)and the swimming distances(F＝3.850,P＜0.05)of rats in four different groups had statistically significant differences.Compared with the IR group,the escape latency of the HRW+IR group was significantly decreased at 3,4,5 d after irradiation(P＜0.05),and the swimming distance of this group became much longer(P＜0.05).The levels of GSH,8-OHdG and MDA in these four groups had statistically significant differences(F＝6.450,5.033,4.113,P＜0.05).Compared with IR group,the concentration of GSH was increased(P＜0.05),but MDA and 8-OHdG decreased(P＜0.05)in the brain tissue of HRW+IR group,and the expressions of caspase-3,caspase-9 and bax genes were reduced(t＝2.956,3.087,5.246,P＜0.05),while the expression of bcl-2 gene was enhanced(t ＝-3.640,P ＜0.05)in the HRW+IR group.Conclusions Hydrogen-rich water attenuates the oxidative damage of ionizing radiation by neutralizing oxyhydrogen free radicals and thus protects brain from radiation damage.