This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Female ; Mice ; Animals ; Glucose Transporter Type 1/genetics* ; Network Pharmacology ; Animal Experimentation ; Saline Solution ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Signal Transduction ; Glycolysis ; RNA, Messenger ; Neoplasms/drug therapy* ; Molecular Docking Simulation

This study aims to observe the effect and explore the mechanism of Qirong Tablets in the treatment of premature ovarian insufficiency(POI) in mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly divided into normal group, model group, positive control group, Qirong Tablets low-, medium-and high-dose group. The normal group was intraperitoneally injected with the same amount of normal saline, and the other groups were intraperitoneally injected with cyclophosphamide 120 mg·kg~(-1)·d~(-1) once to establish a POI animal model. After the model was successfully established, the low-, medium-and high-dose groups of Qirong Tablets were administered orally with 0.6, 1.2, 2.4 mg·kg~(-1)·d~(-1) respectively. The positive control group was given 0.22 mg·kg~(-1)·d~(-1) Clementine Tablets by intragastric administration, and the normal group and model group were given intragastric administration with the same amount of normal saline, and the treatment was 28 d as a course of treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with the normal group, the modeling of POI caused loose or destroyed ovarian tissue with vacuolar structures, edema and fibrosis in the ovarian interstitium, disordered or loose arrangement of granulosa cells, and reduced normal follicles. Compared with the model group, drug interventions restored the ovarian tissue and follicles at all the development stages and reduced atretic follicles. Compared with the normal group, the modeling of POI lowered the serum level of E_2 and AMH(P<0.01), and elevated the level of FSH and LH(P<0.01). Compared with the model group, high-dose Qirong Tablets elevated the levels of E_2 and AMH(P<0.05), and lowered the levels of FSH and LH(P<0.05). Compared with the normal group, the modeling of POI up-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.01). Compared with the model group, low-, medium-, and high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.05). In conclusion, Qirong Tablets can up-regulate the expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, thereby delaying ovarian aging, improving reproductive axis function, and strengthening ovarian reserve capacity, which may be associated with the inhibition of PI3K/Akt/HIF-1 pathway.
Humans ; Mice ; Female ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein ; Phosphatidylinositol 3-Kinases/metabolism* ; Caspase 3/metabolism* ; Saline Solution/therapeutic use* ; Signal Transduction ; Granulosa Cells ; Primary Ovarian Insufficiency/drug therapy* ; Follicle Stimulating Hormone/therapeutic use* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.
Animals ; Brain/drug effects* ; Glutathione ; Inflammation ; Kidney/drug effects* ; Kidney Diseases/chemically induced* ; Male ; Mercuric Chloride/therapeutic use* ; Mercury/urine* ; Mercury Poisoning/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/therapeutic use* ; Unithiol/therapeutic use*

This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 μg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.
AMP-Activated Protein Kinases ; Animals ; Arisaema/chemistry* ; Bile ; Chloral Hydrate ; Cold-Shock Response/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism ; Heat Stroke/therapy* ; Hot Temperature ; Male ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; Syndrome ; TOR Serine-Threonine Kinases ; Thyroxine ; Water

OBJECTIVE: To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism. METHODS: A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44). RESULTS: BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01). CONCLUSIONS BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.
Animals ; Male ; Mice ; Antineoplastic Agents/therapeutic use* ; beta Catenin/metabolism* ; Diarrhea/drug therapy* ; Fluorouracil/pharmacology* ; Intestinal Mucosa ; Mucositis/metabolism* ; Pentobarbital/therapeutic use* ; Proliferating Cell Nuclear Antigen/metabolism* ; Saline Solution

PURPOSE: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP). METHODS: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3. RESULTS: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09). CONCLUSION Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.
Brain Edema ; Brain Injuries, Traumatic/drug therapy* ; Diuretics, Osmotic/therapeutic use* ; Humans ; Intracranial Hypertension/etiology* ; Intracranial Pressure ; Mannitol/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Saline Solution, Hypertonic ; Sodium Lactate

OBJECTIVETo investigate the effect of Hydrogen-saline on Lung Injury and HO-1 Expression in The Lung Tissue of Acute Paraquat-intoxicated mice.

METHODS108 male clean-grade mice were divided randomly into 3 groups: normal control group (n = 8), PQ group (n = 50) and PQ HN group (n = 50), PQ group were lavaged with 20% PQ (50 mg/kg). PQ+Hyclrogen saline group were intxaperitoneal injected with 5 ml/kg saturated hydragen saline after lavaged, 2 times/d. We observe its performance after the poisoning, The lung tissue were taken to HE stained, MDA and SOD activity of lung tissue homogenate were detected, HO-1 activity were observed by immunohistochemistry and western method at 6 h, 1 d, 3 d, 7 d and 14 d.

RESULTSmice came to shortness of breath, exhaustion and death after poisoned. PQ+hydrogen saline group was more alleviative than PQ group. The lung MDA of PQ group was markedly increased at 6 h and 24 h and SOD was decreased at 6 h, 24 h, 3 d, 7 d, 14 d than normal control group. In Comparison with PQ group, the lung MDA was decreased at 24 h and SOD was increased at 24 h and 3 d (P < 0.05). HO-1 expression trend and distribution in PQ+hydrogen saline group are similar with PQ group, but were significantly higher than that of PQ group and the control group each time point (P < 0.05).

CONCLUSIONOxidative stress plays important roles in lung injury caused by paraquat. Hydrogen-saline may increase expression of HO-1 and alleviate oxidative stress damage in lung.

Acute Lung Injury ; metabolism ; pathology ; Animals ; Heme Oxygenase-1 ; metabolism ; Hydrogen ; Lung ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Membrane Proteins ; metabolism ; Mice ; Oxidative Stress ; Paraquat ; toxicity ; Saline Solution, Hypertonic ; therapeutic use ; Superoxide Dismutase ; metabolism

OBJECTIVEThe mainstay of therapy in patients with septic shock is early and aggressive intravenous fluid resuscitation. However the type of intravenous fluid that would be ideal for managing septic shock has been intensely debated. In this study, the authors observed the effects of 3% hypertonic saline solution compared with normal saline solution as early fluid resuscitation in children with septic shock.

METHODIn this prospective study, 44 septic shock children seen in the intensive care unit (ICU) of the Children's Hospital Affiliated to Capital Institute of Pediatrics were enrolled from January 2012 to January 2014, of whom 33 were male and 11 were female. Patients were randomly divided into two groups: normal saline group (NS group, 24 patients) and 3% hypertonic saline group (HS group,20 patients). There were no significant differences between the 2 groups of patients in age, gender, pediatric critical illness score (PCIS), oxygenation index (OI = PaO2/FiO2), arterial lactate, initial hemodynamic parameters, serum sodium and treatment at time of admission. Patients in NS group received normal saline guided by standard therapy. Those in HS group received 6 ml/kg 3% hypertonic saline as a single bolus over 10 min to 15 min with a maximum of 2 boluses and other standard therapy. Heart rate (HR), mean arterial blood pressure (MAP), arterial lactate, oxygenation index, urine output, serum sodium, lactate clearance rate, PCIS, fluid infusion volume, vasoactive - inotropic score, mechanical ventilation time , as well as incidence of multiple organ dysfunction syndrome (MODS), and 28 days in - hospital mortality were recorded for all patients.

RESULT(1) HR, MAP in both groups were significantly higher after infusion than those on admission. There were no significant difference in HR and MAP at 1h, 3h, 6h and 24h after infusion between NS group and HS group. (2) OI in HS group was significantly higher than that on admission at 3 hours after infusion [(321. 8 ± 50. 7) vs. (296. 5 ± 58. 2) mmHg, t = -2. 50, P = 0. 018 ]), and it was significantly higher at 24 hours after infusion in NS group (325. 7 ± 62. 6) vs. (304. 2 ± 70. 4) mmHg, t = -2.60, P=0.016]. There were no significant differences in OI at 1h, 3h, 6h and 24h after infusion between NS group and HS group. (3) At 1 hour after infusion, serum sodium in HS group was significantly higherthan that in NS group [(138.3 ± 3.8)vs. (135.0 ± 3.5) mmol/L, t=8.77, P=0.005], and then no significant difference at 3h, 6h and 24h after infusion between two groups. (4) At 6 hours and 24 hours after treatment, fluid infusion volume in HS group was markedly less than that in NS group [6 h: (39. 2 13. 9) vs. (60. 8 ± 22. 4) ml/kg, t = 14. 21, P =0. 000; 24 h: (102. 9 ± 27. 7) vs. (130. 6 ± 33. 2 ) ml/kg, t= 8. 85, P = 0. 005]. Urine output had not significant different between the two groups. (5) There were no significant differences in 24h PCIS, 24h lactate clearance rate, vasoactive - inotropic score and mechanical ventilation time between the two groups. The incidence of MODS (80. 0% in HS group, 70. 0% in NS group) and mortality rate(5. 0% in HS group, 8. 3% in NS group) were similar in both groups.

CONCLUSIONThe 3% hypertonic saline was effective as resuscitation fluid in pediatric septic shock with respect to restoration of hemodynamic stability without obvious side effects. Hypertonic saline could more rapidly improve oxygenation and need less fluid infusion volume compared with normal saline.

Arterial Pressure ; Child ; Female ; Fluid Therapy ; Heart Rate ; Hemodynamics ; Humans ; Intensive Care Units ; Male ; Multiple Organ Failure ; Prospective Studies ; Resuscitation ; Saline Solution, Hypertonic ; therapeutic use ; Shock, Septic ; therapy ; Sodium Chloride ; therapeutic use

OBJECTIVETo compare the efficacy of 3% hypertonic saline solution with 20% mannitol in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage.

METHODSAn alternating treatment protocol was used to compare the efficacy of 160 mL 3% hypertonic saline solution (HSS) with 150 mL 20% mannitol for episodes of increased intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage. The dependent variables were the extent and duration of reduction of increased ICP after each event.

RESULTSBoth 3% HSS and 20% mannitol rapidly decreased the ICP in patients with aneurysmal subarachnoid hemorrhage (P <0.01). No difference between two medications in the extent of duration of ICP and reduction of action (P >0.05).

CONCLUSION3% HSS should be considered as the first-line osmotic drug in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage.

Humans ; Intracranial Hypertension ; drug therapy ; Mannitol ; therapeutic use ; Saline Solution, Hypertonic ; therapeutic use ; Subarachnoid Hemorrhage ; drug therapy ; Treatment Outcome

OBJECTIVETo assess the efficacy and safety of inhaled nebulized hypertonic saline (HS) solution in infants with acute bronchiolitis.

METHODTotally 129 patients with acute bronchiolitis (clinical severity score ≥ 4, aged 2-18 months) admitted to the Capital Institute of Pediatrics from November 2012 to January 2013 were enrolled. All the subjects were assigned to receive 1.5 ml compound ipratropium bromide solution for inhalation and 1 ml budesonide firstly, twice a day. Then, the subjects were randomized to receive 2 ml doses of nebulized 5% HS (Group A), 3% HS (Group B) or 0.9% NS (Group C), twice a day. The treatment lasted for 3 days. Clinical severity scores before treatment and 24, 48, 72 h after treatment were documented. Bronchospasm, nausea and emesis were recorded to assess safety.

RESULTA total of 124 patients completed this research.Group A included 40 cases, Group B included 42 cases, Group C included 42 cases. Demographic characteristics, pre-treatment duration and clinical severity score before treatment were similar among the 3 group.Seventy-two hours after treatment, the clinical severity score of Group A, B, and C were 3.5 (1.0) , 4.0 (1.0) and 5.0 (0) . At 24, 48, and 72 h after treatment, the clinical severity score were significantly different among the three groups (χ(2) = 36.000, 51.200, 50.800, P < 0.05) .One patient in Group A got paroxysmal cough everytime as soon as he received 5% HS (6 times).Other 3 patients in Group A got paroxysmal cough once. The incidence of adverse effect of Group A was 3.75% (9/240); no adverse event occurred in other group. The incidence of adverse effect among this three group was significantly different (χ(2) = 19.13, P < 0.01).

CONCLUSIONInhalation of nebulized 5% and 3% hypertonic saline could decrease clinical symptoms of patient with acute bronchiolitis; 5% HS was superior to 3% HS. But 2 ml dose of 5% HS may induce paroxysmal cough.

Administration, Inhalation ; Bronchiolitis ; drug therapy ; pathology ; Bronchodilator Agents ; administration & dosage ; adverse effects ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Cough ; etiology ; Female ; Humans ; Infant ; Ipratropium ; administration & dosage ; chemistry ; therapeutic use ; Male ; Saline Solution, Hypertonic ; administration & dosage ; adverse effects ; therapeutic use ; Severity of Illness Index ; Treatment Outcome