[Quality of life and influencing factors of postoperative accelerated rehabilitation of esophageal cancer patients].

Objective: To explore the quality of life and its influencing factors of enhanced recovery after surgery (ERAS) of esophageal cancer patients. Methods: The quality of life of 134 esophageal cancer patients was assessed using the quality of life assessment scale (EORTC QLQ-C30) developed by the European Cancer Research and Treatment Organization. Student's t test, One-way ANOVA and multiple linear regression statistical methods were used to analyze the effects of sociodemographic and clinical characteristics on patients' quality of life. Results: The overall score of quality of life (74.00) was lower than that of the general population (75.30). However, the scores of emotion and cognition in function dimension (93.97 and 95.77) were better than those of the general population (82.80 and 86.50). The results of fatigue, pain, insomnia and constipation in symptom dimension (14.18, 10.94, 11.69 and 5.72) were better than those of the general population (28.80, 20.50, 20.40 and 10.70). The pathological stage, body mass index and dietary were independent influencing factors for the quality of life of patients with esophageal cancer (P<0.05). Conclusions: ERAS can partially improve the quality of life of esophageal cancer patients. More attention should be paid to the esophageal cancer patients after surgery and take targeted measures to improve their quality of life.

[Effects of myocardial fibrosis on ischemic preconditioning against myocardial ischemia-reperfusion injury in type 2 diabetic rats].

Objective: To assess whether myocardial fibrosis affects the protective efficiency of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion injury (MIRI) in type 2 diabetic rats. Methods: Type 2 diabetic rat model was established. Fifty-four normal and 54 diabetic spragus-dawley (SD) rats were equally divided into 6 groups (n=18) using the random number table method: (1) Control group (C group); (2) Ischemia reperfusion injury (IRI) control group (IRI group); (3) IPC group; (4) Diabetic control group (DC group); (5) Diabetic IRI group (DIRI group); (6) Diabetic IPC group (DIPC group). After the reperfusion, blood samples were obtained for measuring serum concentrations of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) using enzyme-linked immunosorbent assay (ELISA). The myocardial infarction size (IS) was assessed by double staining method with Evan's blue and Triphenyl tetrazolium chloride (TTC), and the myocardial collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed by Masson staining. Results: A stable and effective rat model with long-term diabetes was established in the current study. Compared with the normal rat groups, the CVF and PVCA significantly increased (all P<0.05) in the diabetic rat groups. The levels of CK-MB, cTnI and IS in the IPC group were (6.6±0.8) ng/ml, (0.5±0.1) ng/ml and (25.1±4.7) %, which showed significant decrease compared with (12.3±1.1) ng/ml, (1.2±0.3) ng/ml and (52.3±8.1) % in IRI group (all P<0.05). Among the diabetic rat groups, the CK-MB and cTnI levels in DIPC group were (11.5±0.9) and (1.1±0.1) ng/ml, apparently lower than the levels of (16.6±2.2) and (1.4±0.3) ng/ml in the DIRI group (both P<0.05). Compared with the IPC group, the IS, CK-MB and cTnI levels significantly increased in the DIPC group (all P<0.05). Conclusion: Myocardial fibrosis exists in rats with long-term type 2 diabetes, which weakens the protective effect of IPC on diabetes MIRI.

Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

N-arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective alpha 1-adrenoceptor antagonists.

Novel arylpiperazines were identified as alpha 1-adrenoceptor (AR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a "negative screen" for the test antagonists. Binding to alpha 1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha 1-AR subtype prevalent in the human lower urinary tract(pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha 1D-AR.

Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice.

1. We investigated the cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor mice. The in vitro pharmacology of these agonists was determined at recombinant (human) alpha2-adrenoceptors and at endogenous (dog) alpha2A-adrenoceptors. 2. In wild-type mice, rilmenidine, moxonidine (100, 300 and 1000 microg kg(-1), i.v.) and clonidine (30, 100 and 300 microg kg(-1), i.v.) dose-dependently decreased blood pressure and heart rate. 3. In D79N alpha2A-adrenoceptor mice, responses to rilmenidine and moxonidine did not differ from vehicle control. Clonidine-induced hypotension was absent, but dose-dependent hypertension and bradycardia were observed. 4. In wild-type mice, responses to moxonidine (1 mg kg(-1), i.v.) were antagonized by the non-selective, non-imidazoline alpha2-adrenoceptor antagonist, RS-79948-197 (1 mg kg(-1), i.v.). 5. Affinity estimates (pKi) at human alpha2A-, alpha2B- and alpha2C-adrenoceptors, respectively, were: rilmenidine (5.80, 5.76 and 5.33), moxonidine (5.37, <5 and <5) and clonidine (7.21, 7.16 and 6.87). In a [35S]-GTPgammaS incorporation assay, moxonidine and clonidine were alpha2A-adrenoceptor agonists (pEC50/intrinsic activity relative to noradrenaline): moxonidine (5.74/0.85) and clonidine (7.57/0.32). 6. In dog saphenous vein, concentration-dependent contractions were observed (pEC50/intrinsic activity relative to noradrenaline): rilmenidine (5.83/0.70), moxonidine (6.48/0.98) and clonidine (7.22/0.83). Agonist-independent affinities were obtained with RS-79948-197. 7. Thus, expression of alpha2A-adrenoceptors is a prerequisite for the cardiovascular effects of moxonidine and rilmenidine in conscious mice. There was no evidence of I1-imidazoline receptor-mediated effects. The ability of these compounds to act as alpha2A-adrenoceptor agonists in vitro supports this conclusion.

Tissue selectivity of propranolol derivatives in vivo. A confirmation of in vitro findings.

The beta-adrenergic antagonist activities of a p-toluidide and a p-trifluoromethylanilide derivative of propranolol were tested in intact rats to determine whether the unusual in vitro profiles on myocardium and adipose tissue were found in vivo. The relative potencies of p-toluidide derivatives studied in pithed rats were 1.3 for the rate of change in left ventricular pressure with respect to time (dP/dt) and 4.6 for heart rate (HR) compared to propranolol. The values for p-trifluoromethylanilide were 2.5 (dP/dt) and 4.6 (HR). The SR-isomer of the p-toluidide derivative was 81 times more potent than propranolol in inhibiting effects on dP/dt and 27 times more effective than propranolol on HR, whereas the SS-isomer was 0.17 times (dP/dt) and 0.16 times (HR) as potent as the parent compound. In fasted rats, infusion of isoproterenol resulted in an increase of 10.6 +/- 3.1 mg/dl in plasma non-esterified fatty acid (NEFA) and an increase of 46 +/- 9 mg/dl in glucose. Unlike propranolol, neither the p-toluidide nor the p-trifluoromethylanilide derivative blocked the increase in plasma NEFA, although they both blocked the increase in plasma glucose. It appeared that the p-toluidide and p-trifluoromethylanilide derivatives of propranolol were more selective for the beta 1-adrenergic receptors on the heart as opposed to the beta 1-like adrenoceptors on adipose tissue. These findings were qualitatively and generally quantitatively in agreement with our previous findings in vitro. Therefore, the in vitro data may be useful in predicting atypical and tissue selective in vivo effects of these types of compounds.

Edge extraction by active defocusing.

A novel edge extraction method that employs an active defocusing technique is presented. The method is based on the principle that a Laplacian-of-Gaussian (LOG) operation can be approximated by a Difference-of-Gaussian (DOG) operation. While such an operation is usually done in digital image processing, it can also be very effective conducted in a combination of optical techniques and digital processing. In this edge extraction method, a focused image of an object in a scene is first acquired. The image of the scene is then slightly defocused by changing the focal length of the camera. A real time subtraction operation is applied to subtract the defocused image from the previously acquired image. It produces a residual image that emphasizes abrupt intensity variations. An objective evaluation, called an edge index, is performed on the resulting image. The amount of defocusing is carefully adjusted according to this measurement so that a desired edge image is generated. Boundaries of objects can then be obtained by further enhancement of the edge image. Since this edge detection method is an optical-based process aided by digital processing, it is fast and relatively inexpensive.

Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice.

Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The [14C]antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73% +/- 2%), demethylase (mean = -90% +/- 2%), and nondemethylase (mean = -60% +/- 4%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as 14CO2 was decreased by 50-80% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.