Objective:To explore the effects of Changtong Recipe on levels of intestinal neurotransmitters and inflammatory cytokines in the elderly with functional constipation (FC).Methods:A total of 90 elderly patients with FC meeting the inclusion criteria in the hospital were enrolled between June 2020 and October 2021. According to the principle of random allocation, they were divided into control group (45 cases, treated with oral polyethylene glycol electrolyte powder) and treatment group (45 cases, Changtong Recipe). All were treated for 3 months and followed up for 30 d. Before and after treatment, TCM symptoms were scored. The levels of vasoactive intestinal peptide (VIP) and substance P (SP) were detected by radioimmunoassay. The levels of IL-17A and IL-18 were detected by ELISA. The constipation severity and quality of life were evaluated by clinical constipation scale (CCS) and Patient Assessment of Constipation Quality of Life scale (PAC-QOL). The adverse events during treatment and recurrence during follow-up were recorded. The clinical responsive effect was evaluated.Results:After treatment, there were 44 cases in treatment group and 43 cases in control group included into the statistics. The differences in total response rate between treatment group and control group were statistically significant [97.7% (43/44) vs. 81.4% (35/43); χ2=6.25, P=0.012]. After treatment, scores of TCM symptoms (mental fatigue, shortness of breath and abdominal distension, foreign body sensation in the throat, palpitation, cold extremities) and total score in the treatment group were significantly lower than those in the control group ( t=3.71, 10.25, 2.87, 2.87, 5.68, 26.94, all Ps<0.01), and scores of CCS and PAC-QOL were significantly lower than those in the control group ( t=11.71, 18.84, all Ps<0.001). After treatment, levels of serum VIP [(41.86±1.16) ng/L vs. (35.71±1.97) ng/L, t=17.79] and SP [(42.15±1.90) ng/L vs. (39.53±2.13) ng/L, t=6.06] in treatment group were higher than those in the control group ( P<0.01), while levels of IL-17A [(35.71±5.97 ) pg/L vs. (41.86±5.16) pg/L, t=5.14] and IL-18 [(22.15±3.90) pg/L vs. (26.53±4.13) pg/L, t=5.09] in treatment group were significantly lower than those in the control group ( P<0.01). During treatment, difference in incidence of adverse events between treatment group and control group was not statistically significant [9.1% (4/44) vs. 14.0% (6/43); χ2=0.13, P=0.716]. During the 30d of follow-up, differences in recurrence rate between treatment group and control group were statistically significant [2.3% (1/44) vs. 16.3% (7/43); χ2=5.11, P=0.024]. Conclusion:The Changtong Recipe can improve levels of intestinal neurotransmitters (VIP, SP) and quality of life in elderly patients with FC, reduce levels of inflammatory cytokines (IL-17A, IL-18) and improve clinical curative effect safely.

Purpose To investigate the expression of protein kinase D1 (PKD1) in endometrial carcinoma and normal endometrium,and to investigate its relationship with the clinicopathological features of endometrial carcinoma.Methods Immunohistochemical SP and qRT-PCR was used to detect the mRNA and protein expression of PKD1 in 92 cases of endometrial cancer and 48 cases of normal endometrium,and to analyze the relationship of expression of PKD1 with the tumor differentiation and clinical stage of endometrial carcinoma tissue.Western blot method was used to detect the expression level of PKD1 protein in normal endometrial cell line and endometrial carcinorna cell lines with different degree of differentiation.Results mRNA and protein expression of PKD1 in endometrial carcinoma tissues was significantly higher than those in normal endometrial tissues (P ＜ 0.01),which showing a correlation to the degree of tissue differentiation and clinical pathologic staging.While,the expression level of PKD1 protein in endometrial cancer cell lines was also much higher than that in normal endometrial cells (P ＜ 0.01),and the lower differentiation,the higher level of PKD1 protein expression.Conclusion PKD1 is highly expressed in endometrial cancer patients.The level of PKD1 expression may be an important reference for predicting the malignant degree of endometrial cancer.

Objective To investigate the effect and significance of salidroside on Eag1 expression in mouse cervical cancer xenograft.Methods The mouse subcutaneous xenograft model of cervical cancer U14 cells was established.Forty female Kunming mice were divided into 4 groups according to the random principle,the xenograft group,cisplatinum group,salidroside group and cisplatinum combined salidroside group.Then the mass size was measured by using the vemier caliper everyday.The xenograft tumor weight was measured by using the electronic scale and the tumor inhibiting rate was calculated.The immunohistochemistry method was adopted to verify that the xenograft tumor was undifferentiated squamous cell carcinoma.The tumor surrounding tissue in the xenograft group was taken as the control group.RT-PCR and Western blot were adopted to detect the expression levels of Eag1 mRNA and protein in mouse cervical cancer xenografts in each group.Results Kunming mice renograft tumor model was established by subcutaneous injection of cervical cancer U14 cells,the tumor formation rate was 100％.The tumor volume and tumor weight in the cisplatinum group,salidroside group and combined group were lower than those in the senograft group,the xenograft tumor volume and tumor weight in the combined xenograft group were significantly lower than those in the cisplatinum group and salidroside group (P＜0.05);the expressions of Eag1 mRNA and protein in the xenograft group,cisplatinum group and combined group were significantly higher than those in the control group,while which in the cisplatinum group,salidroside group and cisplatinum combined salidroside group were significantly lower than those in the xenograft group,the Eag1 expression level in the combined group was lower than that in the cisplatinum group and salidroside group,the difference was statistically significant(P＜ 0.05).Conclusion Salidroside can inhibit the growth of cervical cancer xenograft and Eag1 expression,and the effect in the combined use with cisplatinum is more significant.

BACKGROUND:Tumor stem cels are the root of cancer recurrence and metastasis, so clinical researches should focus on the effects of different treatments on tumor stem cels.
OBJECTIVE:To explore the effects of endocrine therapy and chemotherapy on stem cels in patients with breast cancer.
METHODS:After recovery and cultivation of estrogen receptor-positive human breast cancer cel lines MCF-7, passage 3 cels in logarithmic phase were selected and divided into three groups containing control, estradiol and estradiol with tamoxifen groups. The estradiol group was divided into three subgroups: 10-7, 10-8 and 10-9 mol/L estradiol was added into the medium, respectively; the estradiol with tamoxifen group was divided into three subgroups: 10-7, 10-8 and 10-9 mol/L estradiol with 10-6 mol/L tamoxifen were added into the medium, respectively. The same amount of absolute ethyl ethanol was added into the medium of control group. Fifteen female patients with late recurrence and metastasis of breast cancer received chemotherapy as recurrence and metastasis group. Another 15 healthy volunteers were selected as healthy control group.
RESULTS AND CONCLUSION:The proportion of CD44+CD24-/lowcel subsets in the estradiol and estradiol with tamoxifen groups was significantly higher than that of the control group (P < 0.05), and the proportion of CD44+CD24-/low cel subsets in the estradiol group was significantly higher than that of the estradiol with tamoxifen group at the same concentration (P< 0.05). The proportion of CD44+CD24-/lowcel subsets had no significant differences among groups at 10 and 20 days of culture (P < 0.05). The proportion of CD44+CD24-/low cel subsets significantly increased in MCF-7 cels after 24-hour intervention with different chemotherapy drugs. But only the proportion of CD44+CD24-/low cel subsets in the paclitaxel and doxorubicin groups was significantly higher than that of the control group after 20-day intervention (P < 0.05). Besides, the proportion of CD44+CD24-/low cel subsets in the peripheral blood of healthy volunteers was significantly lower than that of the recurrence and metastasis group (P < 0.05). Among 15 patients with late recurrence and metastatic of breast cancer, 9 had stable disease, 5 had partial remission, 1 had failed chemotherapy and cancer progression. Moreover, the proportion of CD45-CD44+CD24-/low cel subsets in the peripheral blood of patients sensitive for chemotherapy was significantly lower than that before treatment (P < 0.05). In conclusion, both endocrine therapy and chemotherapy exert a certain effect on the CD44+CD24-/low cel subsets of breast cancer positive for estrogen receptor. Given that CD44+CD24-/low cel subsets in MCF-7 cels resist chemotherapy drugs, the proportion of CD45-CD44+CD24-/low cels in the peripheral blood of patients sensitive for chemotherapy is decreased.

BACKGROUND: Procyanidins is a kind of polyphenol compounds in regnum vegetable, which is composed of different quantities of catechin and epicatechin. Studies show that procyanidins plays a role on protecting vascular endothelium, scavenging free radicals, resisting platelet aggregation, and reducing capillary permeability. Thus, procyanidins has obviously functions of reducing blood pressure, anti-oxidant activity, anti-edema, preventing coronary heart disease and atherosclerosis.
OBJECTIVE: To study the vasorelaxant effect of procyanidins on pulmonic rings and its mechanisms.
METHODS: Rabbit thoracic pulmonary arteries were isolated. Pre-contracted with noradrenalin (1×10-6 mol/L) and their responses to different concentrations of procyanidins (0.625, 1.25, 2.5 mg/L) were investigated. After removal of the endothelium of pulmonary artery smooth muscle, the effects of different signaling pathway inhibitors on procyanidins-induced relaxation, including nitric oxide synthase inhibitor Nω-Nitro-L-arginine (1×10-4 mol/L), methylene blue (1×10-5 mol/L), prostaglandin synthase inhibitor indomethacin (1×10-5 mol/L) and blockage of the adrenergicβ-receptor propranolol (1×10-5 mol/L), were also assessed.
RESULTS AND CONCLUSION: (1) Procyanidins did not change the resting tension of rabbit’s pulmonic rings, but caused an obvious dose-dependent relaxation in 1×10-6 mol/L noradrenalin-precontracted pulmonic rings (r=0.69, P < 0.001). (2) The relaxant effect of procyanidins was significantly reduced by removal of endothelium or by treatment with either Nω-Nitro-L-arginine or methylene blue, but not by treatment with prostaglandin synthase inhibitor or blockage of the adrenergic β-receptor. (3) Procyanidins (20 mg/L) dropped the dose-effect curves of noradrenalin, KCl and on pulmonic rings denuded endothelium. Moreover, affinity index of noradrenalin, KCl and CaCl2 decreased (P < 0.01). (4) Procyanidins also inhibited the vasoconstriction caused by noradrenalin in the first phase, but had no impact on the constriction induced by CaCl2 in the second phase. (5) Procyanidins has an endothelium-dependent vasorelaxation on isolated rabbit’s pulmonic rings, which is possibly mediated by nitric oxide/cyclic guanosine monophosphate pathways. Procyanidins blocked receptor-operated and voltage-dependent calcium channels to reduce intracel ular Ca2+, and induced vasorelaxation.

BACKGROUND:Aconitum carmichaeli Debx (ACD) is the tuberous root of Aconium carmicgaekum, used as cardiotonic to restore yang for the treatment of colapse and shock, to warm the kidney and reinforceyang, and to expel cold and promote the flow ofyang-qi. Studies have found that ACD has obviously cardiotonic, antihypertensive, vasodilatory, analgesic, anti-inflammatory and toxic effects. OBJESTIVE: To observe the vasodilatory effects of a water decoction of ACD on rabbit’s aorta rings and its mechanism. METHODS:Rabbits aorta arteries were isolated, pre-contracted with noradrenaline (10-6 mol/L) and their responses to different concentrations of ACD (0.5, 1.0, 2.0, 4.0, 8.0 g/L) were investigated. The effects of removal of vascular endothelium and different signaling pathway inhibitors (Nω-nitro-L-arginine: 1×10-4 mol/L, methylene blue: 1×10-5 mol/L, indomethacin: 1×10-5 mol/L, propranolol: 1×10-5 mol/L) on ACD-induced vasodilation were also assessed. RESULTS AND CONCLUSION:ACD could not change the resting tension of rabbit aortic rings, but ACD treatment resulted in an obvious relaxation in narodrenaline-precontracted aortic rings and the relaxant effect was dose-dependent. The vasodilatory effect of ACD was significantly reduced by removal of endothelium, 1×10-4 mol/L Nω-nitro-L-arginine and 1×10-5 mol/L methylene blue but not reduced by indomethacin and propranolol. In addition, 4 g/L water decoction of ACD did not decrease the dose-response curves of artery rings to narodrenaline or KCl in the absence of endothelial cels. ACD can relax isolated rabbit’s aorta, which may be related to endothelium-released nitric oxide, but has no significant relevance with receptor-operated and voltage-dependent calcium channels.

OBJECTIVETo study the vasodilation effects of the Total alkali Sophora alopecuroids L (TASa) on rabbit thoracic aortic rings in vitro and the possible mechanisms.

METHODRabbit aortic rings were isolated and precontracted with noradrenaline (NA) and then were divided into six groups including control group, TASa group, TASa + 1 x 10(-5) mol x L(-1) indomethacin (Indo), TASa + 1 x 10(-5) mol x L(-1) propranolol (Prop), TASa + 1 x 10(-10 mol x L(-1) N(omega)-nitro-L-arginine (L-NNA), TASa + removal of endothelium. The vasodilation effects of TASa were investigated. In addition, the thoracic aortic rings were pre-treated with TASa (40 mg x L(-1)) and then the thoracic aortic rings were treated with cumulative NA (110(-8)-110(-5) mol x L(-1)), KCl (6.3-100 mmol x L(-1)) or CaCl2 (110(-5)-110(-2) mol x L(-1)). The dose response curves of aortic rings were recorded.

RESULTTASa can relax isolated rabbit aorta and has an obvious concentration-dependent relaxation (r = 0.94, P < 0.01). The relaxant effect of TASa was no significant reducing by removal of endothelium and by treatment with L-NNA, Indo or Prop. In addition, TASa can decrease the dose response curves of aortic rings to NA, KCl or CaCl2.

CONCLUSIONThe vasodilation effects of TASa are related to not only inhibition of intracellular calcium release, but also reduction to calcium flow to the interior of the cell with blockage of calcium channels.

Alkalies ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Myocardial Contraction ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; Rabbits ; Sophora ; chemistry ; Vasodilator Agents ; chemistry ; pharmacology

OBJECTIVETo study the vasorelaxant effect of procyanidin (PC) extracted from grape seeds on rabbit thoracic pulmonic rings in vitro.

METHODRabbits thoracic pulmonic rings were isolated, pre-contracted with noradrenalin (NA) and their responses to different concentrations of PC were investigated. The effects of endothelium and different signaling pathway inhibitors on PC-induced relaxation, including nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA), methylene blue (MB), prostaglandin synthase inhibitor indomethacin (Indo) and blockage of the adrenergic beta-receptor propranolol (Prop), were also assessed.

RESULTPC change the resting tension of rabbit's pulmonic rings but caused an obvious dose-dependent relaxation in 1 x 10(-6) mol x L(-) NA precontracted pulmonic rings (r = 0.69, P < 0.01). The relaxant effect of PC was significantly reduced by removal of endothelium or by treatment with either 1 x 10(-4) mol x L(-1) L-NNA or 1 x 10(-5) mol L(-1) MB, but not by treatment with prostaglandin synthase inhibitor or blockage of the adrenergic beta-receptor. In addition, PC (20 mg x L(-1)) dropped the dose-effect curves of NA, KCl and respectively on pulmonic rings denuded endothelium. PC can also inhibit the vasoconstriction caused by NA in the first phase, but has no impact on the constriction induced by CaCl2 in the second phase.

CONCLUSIONPC has an endothelium-dependent vasorelaxation on isolated rabbit's pulmonic rings, which is possibly mediated by nitric oxide (NO) pathways and blockage of receptor operated and voltage dependent calcium channels.

Animals ; Disease Models, Animal ; Female ; Heart Diseases ; drug therapy ; physiopathology ; Humans ; In Vitro Techniques ; Male ; Proanthocyanidins ; pharmacology ; Pulmonary Artery ; drug effects ; physiopathology ; Rabbits ; Random Allocation ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

BACKGROUND: Recent research has shown that Gastrodia elata Bl (GEB) has a cardiovascular protective effect and relaxes blood vessels with important therapeutic implication to treat coronary heart disease and hypertension. However, the mechanism is still unclear.OBJESTIVE: To study the effect of the water decoction of GEB on noradrenaline (NA) or KC1 precontracted aortic rings and the possible mechanisms.DESIGN: A grouping observational experiment of animal tissue in vitro.SETTING: Department of Physiology, North Sichuan Medical College.MATERIALS: Twelve health New Zealand、White rabbits (2.5-3.0 kg, 7-8 months, SPF, either gender) were provided by the Experimental Animal Center, North Sichuan Medical College. The water decoction of GEB was prepared by Huirentang Drugstore and diluted into 10%, 20%, 40%and 80% solution. The following drugs were used: Nω-nitro-L-arginine (L-NNA, Sigma, USA); Methylene blue (MB, Merck, Germany); Acetylcholine (ACh) and Propranolol (Prop) (The Second Beijing Pharmaceutical Company, China); Indomethacin (Indo, Jingsu Taicang Pharmaceutical Company, China).METHODS: The experiment was performed in the Institute of Materia Medica, North Sichuan Medical College between January 2006 and January 2007. Rabbit smooth muscles of aortic rings were isolated and precontracted with NA. The thoracic aortic rings were treated with GEB with cumulative concentrations of 1.0,2.0,4.0,8.0 and 16g/L respectively. The aortic tings were treated with one of the following signaling inhibitors for 15 minutes, including 1×104mol/L L-NNA, 1×10-5mol/L MB, 1×10-5mol/L Indo and 1×10-5mol/L Prop. The changes of tension in aortic rings were recorded using a force transducer and processed by BL-410 Experimental System of Biological Function. The aortic rings were incubated with 8g/L GEB followed by the NA and KCl dose response experiments.MAIN OUTCOME MEASURES: Blood vessel tension ex vivo.RESULTS: GEB did not change the resting tension of rabbit aortic rings, but GEB treatment resulted in an obvious relaxation in NA-precontracted aortic rings (r=0.85, t=18.45, P＜0.01) and the relaxant effect was dose-dependent. The relaxant effect of GEB was significantly reduced by removal of endothelium and by treatment with 1×10-4mol/L nitric oxide synthase inhibitor L-NNA (1×10-4mol/L), or 1×10-5mol/L guanylyl cyclase inhibitor methylene blue (1×10-5mol/L MB), but not by treatment with prostaglandin synthase inhibitor of blockage of the adrenergic β-receptor (1×10-5mol/L Prop). In addition, GEB (8g/L) decreased the dose response curves of aortic rings to NA or KCl in the absence of endothelial cells, and changed the PD2 values for NA from (6.90±0.93)mol/L in control group to[(5.61±0.70)mol/L, t=2.41, P＜0.05] and for KCl from (1.53±0.55) mmol/L in control group to (1.10±0.25)mmol/L, t=3.82, P＜0.05] respectively.CONCLUSION: GEB can relax isolated rabbit aorta not only in an endothelium-dependent, nitric oxide involved manner, but also is related to blockage of receptor-operated and potential-dependent calcium channels.

Objective To study the mechanism of Shoucong to prevent and cure Alzheimer's disease by observing the effect of shoucong capsule on total autioxidative capacity (TAOC), Lipofuscin (LIP) in AD rat brain tissue and blood, and brain tissue pathological changes. Methods Male wistar rats were randomly divided into 5 group:blank compared group, model compared group, Naofukang group, Shoucong Capsule (low, high dose) group. AD compound model rats were made by injected with D-galactose on the neck of rats, then injected with scopolamine in the intraperiton of rats. They were prevented and cured with Shoucong Capsule. TAOC, LIP level in rat brain tissue and blood were examined with spectroscopic analysis, brain tissue pathological changes were observed under light microscope. Results Compared with AD model group, Shoucong Capsule enhanced TAOC level in rat brain tissue and blood, deceased LIP level in rat brain tissue, and lessened the pathological injury of dementia rats. Conclusions Enhancing TAOC level and deceasing LIP level in brain tissue and blood may be one of the mechanism for Shoucong Capsule to prevent and cure Alzheimer's disease.