Single-crystal growth, structure and thermal transport properties of the metallic antiferromagnet Zintl-phase ß-EuIn2As2.

Zintl-phase materials have attracted significant research interest owing to the interplay of magnetism and strong spin-orbit coupling, providing a prominent material platform for axion electrodynamics. Here, we report the single-crystal growth, structure, magnetic and electrical/thermal transport properties of the antiferromagnet layer Zintl-phase compound ß-EuIn2As2. Importantly, the new layered structure of ß-EuIn2As2, in rhombohedral (R3̄m) symmetry, contains triangular layers of Eu2+ ions. The in-plane resistivity ρ(H, T) measurements reveal metal behavior with an antiferromagnetic (AFM) transition (TN ∼ 23.5 K), which is consistent with the heat capacity Cp(H, T) and magnetic susceptibility χ(H, T) measurements. Negative MR was observed in the temperature range from 2 K to 20 K with a maximum MR ratio of 0.06. Unique 4f7J = S = 7/2 Eu2+ spins were supposed magnetically order along the c-axis. The Seebeck coefficient shows a maximum thermopower |Smax| of about 40 µV K-1. The kink around 23 K in the Seebeck coefficient originates from the effect of the antiferromagnetic phase on the electron band structure, while the pronounced thermal conductivity peak at around 10 K is attributed to the phonon-phonon Umklapp scattering. The results suggest that the Eu2+ spin arrangement plays an important role in the magnetic, electrical, and thermal transport properties in ß-EuIn2As2, which might be helpful for future potential technical applications.

[A preliminary study on the prevention of hemorrhage after laparoscopic pancreaticoduodenectomy by wrapping gastroduodenal artery stump in the left external liver lobe and the left caudate lobe].

Objective: To investigate the safety and efficacy of embedding the stump of gastroduodenal artery between the left lateral lobe of the liver and the left caudate lobe to prevent bleeding after laparoscopic pancreaticoduodenectomy. Methods: The clinical data of 41 patients who underwent laparoscopic pancreaticoduodenectomy at the second Hospital of Hebei Medical University from October 2021 to April 2022 were analyzed retrospectively.There were 27 males and 14 females, aged (63.0±9.2)years (range: 48 to 78 years), and the body mass index was (24.1±3.2)kg/m2 (range: 15.4 to 31.6 kg/m2). After routine laparoscopic pancreaticoduodenectomy, the stump of gastroduodenal artery was embedded between the left lateral lobe and the left caudate lobe of the liver, and the hepatic parenchyma of the left lateral lobe and the left caudate lobe were sutured with absorbable sutures.The occurrence and recovery of postoperative complications (pancreatic fistula, biliary fistula, postoperative abdominal bleeding, abdominal infection, liver abscess) were observed. Results: All the operations of 41 patients were completed successfully.The operation time was (277.5±52.0) minutes (range: 192 to 360 minutes). The entrapment time of gastroduodenal artery stump was (3.1±0.6) minutes (range: 2.3 to 4.2 minutes), and the intraoperative blood loss (M(IQR)) was 300 (200) ml (range: 50 to 800 ml).The results of ultrasound examination of hepatic artery on the first day after operation showed that the blood flows of hepatic artery were unobstructed.Postoperative pancreatic fistula occurred in 3 cases, including grade B pancreatic fistula in 2 cases (1 case with abdominal infection) and biochemical leakage in 1 case. Three patients with pancreatic fistula were discharged successfully after continuous abdominal drainage. There was no biliary fistula, abdominal bleeding, abdominal infection, liver abscess or postoperative liver dysfunction. Conclusion: The encasement of the gastroduodenal artery stump by the left outer and left caudate lobes of the liver may be an effective way to prevent bleeding from the rupture of the gastroduodenal artery stump after laparoscopic pancreatoduodenectomy, which is easy and safe to perform.

[The application of 3D bioprinting in ophthalmology].

On the basis of 3D printing technology, 3D bioprinting has emerged with great development potential and good prospects in the field of medicine and tissue engineering. With this technique, different types of cells and biomaterials can be precisely incorporated into 3D anatomical structures, achieving tissue substitutes with superior structures or functions. In recent years, great progress has been made in the application of 3D bioprinting in ophthalmology. This article reviews not only the differences between 3D printing and 3D bioprinting, but also the development, types, characteristics, application, and prospects of 3D bioprinting in the production of eye tissue engineering materials.

Thermal Dynamics of Charge Density Wave Pinning in ZrTe_{3}.

Impurity pinning has long been discussed to have a profound effect on the dynamics of an incommensurate charge density wave (CDW), which would otherwise slide through the lattice without resistance. Here, we visualize the impurity pinning evolution of the CDW in ZrTe_{3} using the variable temperature scanning tunneling microscopy. At low temperatures, we observe a quasi-1D incommensurate CDW modulation moderately correlated to the impurity positions, indicating a weak impurity pinning. As we raise the sample temperature, the CDW modulation gets progressively weakened and distorted, while the correlation with the impurities becomes stronger. Above the CDW transition temperature, short-range modulations persist with the phase almost all pinned by impurities. The evolution from weak to strong impurity pinning through the CDW transition can be understood as a result of losing phase rigidity.

[Retrospective investigation of spontaneous bloody tears: a report of 27 cases].

Objective: To summarize clinical experience on the clinical feature, etiology and treatment of patients with spontaneous bloody tears as the initial symptom. Methods: Retrospective series of case studies. The clinical data and follow-up data of 27 cases of bloody tears as the first symptom in Lacrimal Center of Ophthalmology, the Third Medical Center of Chinese PLA General Hospital from June 2015 to December 2018 were reviewed. The clinical feature, specific cause, diagnosis, treatment and prognosis of these cases were evaluated. Results: A total of 27 cases were collected in this study. The patients were 10 males (37.0%) and 17 females (63.0%), including 21 adults (≥ 18 years old, 77.8%) and 6 minors (<18 years old, 22.2%). There were 22 monocular cases (81.5%) and 5 binocular cases (18.5%). Five cases (18.5%) were bleeding from the eye and other parts of the body, and 22 cases (81.5%) were bleeding only from the eye. There were 19 cases (70.4%) with hematic epiphora and secretions from the punctum, 3 cases (11.1%) with blood-stained tears, and 7 cases (25.9%) with blood-like tears. With regard to etiology, 6 cases (22.2%) were combined with systemic lesions, one of which was granulomatosis with polyangiitis and five of which (<18 years old) were idiopathic bloody tears. Twenty-one cases (77.8%) were local lesions, including 18 cases only involving the lacrimal system, 2 cases only involving the ocular surface, and 1 case involving both the lacrimal system and the ocular surface. Among the 21 cases with local lesions, 5 cases were induced by foreign body, 6 cases were induced by simple inflammation, and 10 cases were induced by tumor including 1 case with conjunctival benign tumor and 9 cases with tumor of the lacrimal system (5 with malignant tumor and 4 with benign tumor). Patients with idiopathic bloody tears received psychological and medical treatment, and interictal discharge was lengthened. One case of granulomatosis with polyangiitis was treated by trans-nasal endoscopic dacryocystorhinostomy. With the recurrence of granulomatosis and polyangiitis, bloody tears recurred after surgery. One patient with conjunctival hemangioma was untreated. Lesions in the lacrimal duct system were removed and dacryocystorhinostomy was performed. In this study, 2 patients (1 with small cell neuroendocrine carcinoma and 1 with adenoid cystic adenocarcinoma) died and the other had a good prognosis. Conclusions: Among the cases of bloody tears, adults and local lesions are more common. Most of the lesions are located in the lacrimal system and are tumors. The main treatment is to remove the lesions, and if necessary, to expand the resection and reconstruct the lacrimal duct. Idiopathic bloody tears occur in minors, who are gave psychotherapy and necessary medical treatment. (Chin J Ophthalmol, 2020, 56: 53-58).

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.

Stover return and nitrogen application affect soil organic carbon and nitrogen in a double-season maize field.

Cultivation techniques have an important influence on grain yield of maize. This experiment investigated the effect of stover return (SR) and different nitrogen (N) application rate on soil organic carbon (SOC) composition, soil nutrient and maize yield. Different nitrogen application rate 100 (N100), 150 (N150), 200 (N200), 250 (N250) or 300 (N300) kg ha-1 applied to the maize field with stover return and without stover return traditional planting (TP) method. Nitrogen application rate and stover return affected the SOC, labile organic carbon (LOC), microbial biomass (MBC), NO3 - -N, NH4 + -N and maize yield. Soil N, soil carbon content and maize yield of SR were all higher than TP. The SOC content of SR and TP were 9.67 and 9.19 g kg-1 , respectively. Nitrogen application was significantly and positively correlated with soil MBC, LOC, SOC, NO3 - -N, NH4 + -N and yield. The maximum values of SOC composition, soil nutrients and maize yield were reached at SR with 250 kg ha-1 . Stover return with application of N 250 kg ha-1 significantly increased the growth attribute and maize yield in subtropical region compared with traditional planting.

The effect of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

Cytoplasmic dynein is a multi-subunit complex that includes cytoplasmic dynein-1 (dynein1) and cytoplasmic dynein-2 (dynein2). It participates in various basic cellular processes, including nuclear migration, mitotic spindle organization, chromosome separation during mitosis, and the location and function of numerous intracellular organelles. Retinal photoreceptor cells are terminally differentiated neurons that cannot regenerate and cannot be replaced once lost. It is thus crucial to study their development to facilitate the generation and improvement of photoreceptor disease treatments. The outer segment (OS) of photoreceptor cells is a specific sensory cilium. An increasing number of studies have shown that cytoplasmic dynein plays an essential role in the development of retinal photoreceptor cells. To date, people have done a lot of studies on the various functions of dynein in cells and have a very detailed understanding. However, the role of dynein in retinal photoreceptor cells has not been summarized in detail. This article summarizes the currently available knowledge relating to the effects and mechanisms of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

Urinary microRNAs miR-15b and miR-30a as novel noninvasive biomarkers for gentamicin-induced acute kidney injury.

MicroRNAs serve as potential biomarkers in various pathological models, and are stable and detectable in biofluids. We investigated the urinary microRNA expression profile in a gentamicin-induced acute kidney injury canine model using RNA sequencing. A total of 234 differentially expressed microRNAs were screened after 12 consecutive days of gentamicin administration (P < 0.05). Six candidate microRNAs (miR-15b, -15b-3p, -16, -30a, -30a-3p, and -30c-2-3p) were selected according to a set criterion, and validated by real-time quantitative PCR. The diagnostic values of these six candidate microRNAs were better than the traditional serum biomarkers (all P < 0.05). Further, using receiver operating characteristic curve analysis, we found that miR-15b and -15b-3p were superior to urinary kidney injury molecule-1 (both P < 0.05). Moreover, miR-15b and -30a levels in the urine samples significantly correlated with their respective levels in the kidney tissue samples (r=0.512 and 0.505, respectively, both P < 0.05). Our data concluded that miR-15b and -30a may be promising biomarkers for renal toxicity.

[Clinical characteristics of recurrent appendicitis].

Objective: To analyze clinical characteristics of recurrent appendicitis. Methods: A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images. Results: Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ(2)=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ(2)=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ(2)=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10(9)/L vs. (11.5±4.5)×10(9)/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ(2)=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ(2)=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ(2)=4.880, P=0.027). Conclusions: Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Improved prediction of subcellular location for apoptosis proteins by the dual-layer support vector machine.

Apoptosis proteins play an important role in the development and homeostasis of an organism. The accurate prediction of subcellular location for apoptosis proteins is very helpful for understanding the mechanism of apoptosis and their biological functions. However, most of the existing predictive methods are designed by utilizing a single classifier, which would limit the further improvement of their performances. In this paper, a novel predictive method, which is essentially a multi-classifier system, has been proposed by combing a dual-layer support vector machine (SVM) with multiple compositions including amino acid composition (AAC), dipeptide composition (DPC) and amphiphilic pseudo amino acid composition (Am-Pse-AAC). As a demonstration, the predictive performance of our method was evaluated on two datasets of apoptosis proteins, involving the standard dataset ZD98 generated by Zhou and Doctor, and a larger dataset ZW225 generated by Zhang et al. With the jackknife test, the overall accuracies of our method on the two datasets reach 94.90% and 88.44%, respectively. The promising results indicate that our method can be a complementary tool for the prediction of subcellular location.

Prediction of protein structure class by coupling improved genetic algorithm and support vector machine.

Structural class characterizes the overall folding type of a protein or its domain. Most of the existing methods for determining the structural class of a protein are based on a group of features that only possesses a kind of discriminative information for the prediction of protein structure class. However, different types of discriminative information associated with primary sequence have been completely missed, which undoubtedly has reduced the success rate of prediction. We present a novel method for the prediction of protein structure class by coupling the improved genetic algorithm (GA) with the support vector machine (SVM). This improved GA was applied to the selection of an optimized feature subset and the optimization of SVM parameters. Jackknife tests on the working datasets indicated that the prediction accuracies for the different classes were in the range of 97.8-100% with an overall accuracy of 99.5%. The results indicate that the approach has a high potential to become a useful tool in bioinformatics.

Influence of guanidine on proteinase K resistance in vitro and infectivity of scrapie prion protein PrP(Sc).

As the scrapie prion protein PrP(Sc) is rich in beta-sheets it aggregates into prion rods, which show infectivity and proteinase K (PK) resistance. Consequently, dissociation of prion rods and breakdown of beta-sheets in PrP(Sc) by denaturation results in loss of both infectivity and PK-sensitivity. In this study, the effects of guanidine (Gdn), which solubilizes and denatures proteins by breaking down their higher structure, on the solubility, the PK-resistance in vitro and the infectivity of PrP(Sc) of scrapie strain 263K was examined. The infectivity was assayed by intracerebral inoculation into hamsters. Brain tissues of scrapie-infected hamsters were used for preparation of homogenates and crude extracts of PrP(Sc). A treatment of PrP(Sc) with Gdn enhanced its PK-sensitivity in a dose-dependent manner. The PK-resistance in vitro of PrP(Sc) denatured with lower concentrations of Gdn (<2.5 mol/l) could partially resume by renaturation. Gdn markedly reduced or, at higher concentrations, even destroyed the infectivity of PrP(Sc). On the other hand, the infectivity of PrP(Sc) inactivated by denaturation could be partially restored by renaturation. These results confirmed our assumption that all the alternations in the PK-resistance and the infectivity of PrP(Sc) caused by Gdn resulted from changes in its higher structure. However, it should be emphasized that a complete loss of PK-resistance of PrP(Sc) may not necessarily mean its full non-infectivity.

Enrichment of regulatory T-cells in blood of patients with multidrug-resistant tuberculosis.

OBJECTIVE: To measure the percentage of regulatory T-cells (Treg) and the expression of signalling molecules in these cells from the peripheral blood of patients with multidrug-resistant tuberculosis (MDR-TB). DESIGN: Patients with drug-susceptible tuberculosis (S-TB), MDR-TB and healthy controls (HCs) were recruited into the study. Levels of CD4(+)CD25(+)Foxp3(+) Treg cells from peripheral blood, and programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible costimulatory (ICOS) molecule expression in the cells were measured using flow cytometry. Suppression mediated by Treg cells was assessed in carboxyfluorescein succinimidyl ester (CFSE) based suppression assays with autologous CD4(+)CD25(-) T-effector (Teff) cells. RESULTS: Presence of Mycobacterium tuberculosis resulted in a higher proportion of Treg cells in S-TB patients than in HCs, and even higher levels in MDR-TB patients. Moreover, Treg cells in MDR-TB patients constitutively expressed high-level PD-1, CTLA-4 and ICOS. In addition, when cultured with activated CD4(+)CD25(-) Teff cells, Treg cells potently suppressed proliferation of Teff cells. CONCLUSIONS: The high level of Treg cells found in the peripheral blood of tuberculosis patients may partly explain the poor immune response against M. tuberculosis, and could be a marker of MDR-TB.

Effects of mitoxantrone on action potential and membrane currents in isolated cardiac myocytes.

1. The effects of mitoxantrone (MTO), an anticancer drug, on the membrane electrical properties of cardiac myocytes were investigated using the whole-cell clamp technique. 2. In isolated guinea-pig ventricular myocytes, 30 microM MTO induced a time-dependent prolongation of action potential duration (APD) which was occasionally accompanied by early afterdepolarizations. APD prolongation was preserved in the presence of 10 microM tetrodotoxin and showed reverse rate-dependence. 3. Both the inward rectifier K+ current (I(KI)) and the delayed rectifier K+ current (I(K)) of guinea-pig ventricular myocytes were significantly depressed by 30 microM MTO. The rapidly activating component of I(k) (I(Kr)) seemed to be preferentially blocked by MTO. The transient outward current was not affected by MTO in rat ventricular myocytes. 4. Thirty microM MTO had no direct effect on the L-type Ca2+ current (I(Ca(L))), but reversed the inhibitory effect of 1 microM carbamylcholine but not the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (1 microM) on I(Ca(L)) enhanced by 50 nM isoprenaline in guinea-pig ventricular myocytes. In guinea-pig atrial mycotyes, 30 microM MTO inhibited by 93% the muscarinic receptor gated K+ current (I(K,ACh)) evoked by 1 microM carbamylcholine, whereas I(K,ACh) elicited by 100 microM GTPgammaS, a nonhydrolysable GTP analogue, was only decreased by 12%. 5. The specific binding of [3H]QNB, a muscarinic receptor ligand, to human atrial membranes was concentration-dependently displaced by MTO (1-1000 microM). 6. In conclusion, MTO blocks cardiac muscarinic receptors and prolongs APD by inhibition of I(KI) and I(Kr). The occasionally observed early afterdepolarizations may signify a potential cardiac hazard of the drug.

Inhibitory effects of berberine on ATP-sensitive K+ channels in cardiac myocytes.

The effects of berberine on cardiac action potentials were measured in isolated guinea-pig papillary muscles exposed to hypoxia and cromakalim using the standard microelectrode technique. In addition, the patch clamp technique was used to determine the effects of berberine on cromakalim-induced outward currents in isolated ventricular myocytes and on ATP-sensitive K+ (KATP) channels in inside-out membrane patches. Berberine, at 3 microM significantly inhibited, while at 100 microM completely blocked the shortening of action potential duration and effective refractory period induced by hypoxia or cromakalim (100 microM). Under the whole-cell voltage clamp conditions, berberine (3-100 microM) attenuated or even abolished the cromakalim-elicited outward K+ currents. Berberine (3-100 microM) inhibited KATP channel activity in a concentration-dependent fashion in inside-out membrane patches exposed to 0.1 mM ATP. This inhibition appeared to be mainly due to a decrease in the open channel probability without affecting unitary conductance or the time constants for open and closed channel times. Glibenclamide (10 microM) partially blocked the hypoxia-evoked but fully reversed the cromakalim-evoked abbreviation of action potential duration and effective refractory period. Both the whole-cell outward K+ currents induced by cromakalim and the opening of single KATP channels induced by the low intracellular ATP concentration were also completely abolished by 10 microM glibenclamide. We conclude that berberine is a blocker of the cardiac KATP channel. The reported beneficial effect of berberine on ischemia-induced arrhythmias is likely attributed to its inhibition of KATP channel activation and subsequent shortening of action potential duration and effective refractory period during ischemia.

Effects of doxorubicinol on excitation--contraction coupling in guinea pig ventricular myocytes.

The cardiotoxicity of the anticancer drug doxorubicin may be related to its main metabolite doxorubicinol. In this study, the acute effects of doxorubicinol on excitation-contraction coupling in isolated guinea pig ventricular myocytes were investigated and compared with doxorubicin using the whole-cell patch-clamp-, fura-2 fluorescence- and cell-edge tracking techniques. Both drugs were applied intracellularly by diffusion from the patch electrode for 15--20 min. Doxorubicin (100 microM) prolonged the action potential duration (APD) by 31% and enhanced cell shortening by 26%. Contrary to doxorubicin, doxorubicinol (10 microM) shortened APD by 25% and decreased cell shortening by 31%. APD shortening by doxorubicinol was due to an increase of the delayed rectifier K(+) current. Neither the inward rectifier K(+) current nor the L-type Ca(2+) current was influenced by doxorubicinol. The decline in cell shortening induced by doxorubicinol was not exclusively due to APD shortening because doxorubicinol reduced the peak Ca(2+) transient by 23% in cells clamped with an action potential of constant duration. Despite opposite effects on APD and contractility, both doxorubicin and doxorubicinol produced a considerable delay in the activation and inactivation of contraction and Ca(2+) transient, compatible with an impaired function of the sarcoplasmic reticulum. It is suggested that doxorubicinol-induced APD shortening may amplify the detrimental effects of both doxorubicin and doxorubicinol on sarcoplasmic reticulum Ca(2+) load and hence on contractile function. The accumulation of doxorubicinol in the cardiac myocytes may play an important role in the time-dependent development of doxorubicin-induced ventricular dysfunction.

[Relation between myocardial cAMP and renin-angiotensin system activation after acute pressure overload].

In order to investigate the relationship between cAMP and myocardial renin-angiotensin system activation after acute pressure overload, an animal model of acute pressure overload was established by constriction of abdominal aorta. It was found that angiotensin converting enzyme (ACE) mRNA and protein expression were increased markedly, ACE activity and angiotensin II content were also elevated significantly in rat heart 1 h after acute pressure overload, and the increases were kept at high level. Meanwhile the myocardial cAMP concentration was increased significantly at 0.5 h, reached the peak at day 5, and returned to normal at day 30 after operation. Then cardiomyocytes were cultured to observe whether ACE gene expression can be induced by cAMP. The results showed that elevation of cAMP content in cultured cardiomyocytes stimulated by isoproterenol (ISO, 0.01 micromol/L) increased ACE mRNA and protein expression, and also increased ACE activity and Ang II content in cultural medium. These results suggest that cAMP plays a role in the mechanism of activation of myocardial renin-angiotensin system induced by pressure overload.

[Effect of heparinoid derived from porcine duodenum on the proliferation of cultured smooth muscle cells].

AIM: To study the antiproliferative effect of haparinoid derived from porcine duodenum (heparinoid) on cultured vascular smooth muscle cells. METHODS: Cultured bovine aortic smooth muscle cells (BASMCs) of 5-10 passages were seeded into 24 and 72-well cluster culture plates and were synchronized by 48 h serum deprivation. Then, the cells were re-stimulated by serum repletion with or without heparinoid. The antiproliferative effect of heparinoid was evaluated by crystal violet staining and MTT assay 72 h after serum repletion. To study the drug action on cytomorphological changes, three kinds of cells [quiescent cells, cells treated with 10% fetal calf serum (FCS) with or without heparinoid] were observed by transmission electron microscopy. After synchronized and re-stimulated as above, BASMCs were treated with heparinoid 0.8 mg.mL-1 at selected points during serum repletion. The cells were harvested at specified times after serum repletion, then cellular DNA contents (to estimate the proportions of cells in different phases of the cell cycle) and the contents of alpha-actin, c-myc and c-fos proteins were measured by flow cytometry. RESULTS: Heparinoid was shown to inhibit the proliferation of BASMCs induced by 10% FCS. The inhibitory effect was weakened when heparinoid was added 2 h after serum repletion, and there was no antiproliferative effect when heparinoid was added 12 h after serum repletion. Electron micrographs showed that cells treated with 10% FCS and heparinoid expressed a contractile phenotype, while cells treated with 10% FCS only expressed a synthetic phenotype. Flow cytometry study showed remarkable increase of alpha-actin, and decrease of c-myc and c-fos proteins in the cells treated with heparinoid. CONCLUSION: Heparinoid was found to inhibit the proliferation of BASMCs. The antiproliferative effect occurred at the early phase of the cell cycle. It might be due to the drug's influence on cell phenotype modulation and the down regulation of c-myc and c-fos proto-oncogenes expression.