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INTRODUCTION: Immune checkpoint inhibitors can cause immune-related toxicity in various systems, with myocarditis being the most severe and life-threatening manifestation. This report presents a case in which myocarditis developed following administration of programmed cell death protein-1 (PD-1) inhibitors therapy. We describe the diagnosis and treatment of this patient in detail. CASE REPORT: We present the case of a 59-year-old female diagnosed with post-operative esophageal cancer and hepatic metastases. The patient underwent second-line treatment with domestically-made PD-1 inhibitor, camrelizumab, in combination with paclitaxel (albumin-bound) and carboplatin for two cycles. During the course of treatment, an electrocardiogram (ECG) revealed ST segment elevation in leads II, III, aVF, V2, V3, and V4, along with T wave changes in leads I and aVL. Laboratory examinations showed abnormal levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). Despite the absence of clinical symptoms, the patient was routinely hospitalized three weeks later. Based on the findings from the ECG, cardiac biomarkers, echocardiography, echocardiogram, cardiac magnetic resonance, and angiography, she was diagnosed with immune-checkpoint-inhibitors-related myocarditis. MANAGEMENT AND OUTCOME: The patient received immunoglobulin (0.5 g/kg/day) and was initially given methylprednisolone (1000 mg/day). Methylprednisolone was gradually reduced to 40 mg/day in 2 weeks. During this time, the levels of biomarkers indicative of myocardial injury also exhibited a simultaneous decline. DISCUSSION: This case highlights the importance of early detection and prompt intervention, including initiating appropriate steroid therapy and discontinuing of immune checkpoint inhibitors. Such measures can effectively prevent morbidity and mortality, ultimately leading to an improved prognosis.

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BACKGROUND: Knowledge of the compatibility between spirodiclofen and the predator Oligota flavicornis is an important aspect for the management of spider mites. RESULTS: We used the age-stage, two-sex life table to assess the effects of spirodiclofen on the life history traits and population growth of O. flavicornis. At the maximum recommended concentration (60 mg a.i. L-1 ) and also at twice the maximum recommended dosage (120 mg a.i. L-1 ), the preadult stages of O. flavicornis were significantly lengthened, while the adult longevity and fecundity decreased significantly. The finite rate (λ), intrinsic rate of increase (r), and net reproduction rate (R0 ) decreased, while the mean generation time (T) was longer after both the 60 and 120 mg a.i. L-1 treatments than it was in the control and 30 mg a.i. L-1 treatments. Life expectancy and reproductive value were higher in the control and 30 mg a.i. L-1 treatment than in the 60 and 120 mg a.i. L-1 treatments; the two higher concentrations were detrimental to the development of O. flavicornis. CONCLUSION: A proper combination of the O. flavicornis and spirodiclofen to control the spider mite, while avoiding the side effect of spirodiclofen, could be achieved based on the knowledge of life tables. © 2018 Society of Chemical Industry.

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The effect of nine constant temperatures on developmental time of Oligota flavicornis (Boisduval and Lacordaire) preying on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae) eggs was determined under laboratory conditions of 75 ± 5% RH and a 16:8 (L:D) h photoperiod. O. flavicornis survival rates were highest between 18 and 30°C, although O. flavicornis eggs developed successfully to adults at 12-32°C, and the developmental durations to adult at the seven temperatures (12, 15, 18, 20, 25, 30, and 32°C) were 114.41, 51.66, 33.45, 23.21, 13.43, 11.54, and 17.18 d, respectively. Two linear and seven nonlinear models (Logan-6 and Logan-10, Taylor, Lactin-1 and Lactin-2, and Brière-1 and Brière-2) were fit to the developmental rates of the immature predatory stages to estimate the thermal constant (K) and critical temperatures. The lower temperature threshold (T0) and K for the immature stages using the common linear model were 9.96°C and 225.73 degree-days and Ikemoto-Takai linear model were 11.01°C and 167.14 degree-days, respectively. The upper temperature threshold values estimated by the Logan-6 and Lactin-1 models were both 34.86°C. The T0 values estimated by the Brière-1 and Brière-2 models were 10.67 and 9.32°C for all immature stages, respectively, and the estimated optimal temperature according to the Brière-2 model was 29.59°C. Therefore, the two linear models and Brière-2 model estimates approximated the actual relationship between the temperature and developmental rate of immature O. flavicornis.

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Tea green leafhoppers (Empoasca spp.) are considered one of the major pests in tea plantations in Asia. They are, however, difficult to monitor due to their size and flying and jumping abilities. In this study, we clarified the identification of the leafhopper species encountered in our study plantations and examined the impacts of sampling methods in estimating population abundance and sex ratio. The natural sex ratio of eggs, nymphs, and adults of tea green leafhopper and the differences between male and female were tested. Despite previous reports that Empoasca vitis (Goethe) was the major leafhopper present in our study area, our results showed that only Empoasca onukii Matsuda was found. Variation in population size over time and bias in sex ratio depending on the sampling methods were found in our monitoring experiments. In general, adult males were more attracted to yellow sticky cards than females. We believe that because female leafhoppers should be the target in pest control, yellow sticky cards may not be the most suitable monitoring or effective control of tea green leafhopper. We demonstrate the importance of understanding the implications of sampling techniques for population estimation and sex ratio bias as well as how temporal variation may affect monitoring results. Precise monitoring should take into consideration the different life histories of male and female.

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Under myocardial microenvironment, bone marrow-derived mesenchymal stem cells (MSCs) can transdifferentiate into cardiomyocytes (CMs). However, the role of histone deacetylase 1 (HDAC1) in this directed differentiation process remains unclear. The current study is to determine the acetylation regulatory mechanisms that may be involved in the directed CM differentiation from MSCs. MSCs isolated from male Sprague-Dawley (SD) rats were marked with Ad-EGFP and co-cultured with CMs. Flow cytometry was used to sort EGFP-positive (EGFP+) MSCs from the co-culture system. Then, the expression of cardiac troponin T (cTnT) in these MSCs was detected by immunofluorescence assay. In addition, HDAC1 levels at different co-culture times were measured by quantitative real-time polymerase chain reaction (QT-PCR) and Western blotting. At 4 days after co-culture with CMs, the MSCs began to expression detectable levels of cTnT. The expression of HDAC1 in CMs was much lower than that in MSCs. After co-culture with CMs, the expression of HDAC1 in MSCs was significantly decreased in a time dependent manner. In addition, our recent study has also identified that knockdown of the HDAC1 could promote the directed differentiation of MSCs into CMs. The results suggest that HDAC1 has a negative correlation with cardiac cell differentiation from MSCs under a myocardial microenvironment. HDAC1 might play an important role in the directed differentiation of MSCs into CMs in heart.

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Failure of the directed differentiation of the transplanted stem cells into cardiomyocytes is still a major challenge of cardiac regeneration therapy. Our recent study has demonstrated that the expression of histone deacetylase 1 (HDAC1) is decreased in bone mesenchymal stem cells (BMSCs) during their differentiation into cardiomyocytes. However, the potential roles of HDAC1 in cardiac cell differentiation of BMSCs, as well as the mechanisms involved are still unclear. In current study, the expression of HDAC1 in cultured rat BMSCs is knocked down by lentiviral vectors expressing HDAC1-RNAi. The directed differentiation of BMSCs into cardiomyocytes is evaluated by the expression levels of cardiomyocyte-related genes such as GATA-binding protein 4 (GATA-4), Nirenberg, Kim gene 2 homeobox 5 (Nkx2.5), cardiac troponin T (CTnT), myosin heavy chain (MHC), and connexin-43. Compared with that in control BMSCs, the expression of these cardiomyocyte-related genes is significantly increased in these HDAC1 deficient stem cells. The results suggest that HDAC1 is involved in the cardiomyocyte differentiation of BMSCs. Knockdown of the HDAC1 may promote the directed differentiation of BMSCs into cardiomyocytes.

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This study is to evaluate the effects of Simvastatin on left ventricular hypertrophy and left ventricular function in patients with essential hypertension. Untreated or noncompliance with drug treatment patients with simple essential hypertension were treated with a therapy on the basis of using Telmisartan to decrease blood pressure (BP). There were 237 patients who had essential hypertension combined with left ventricular hypertrophy as diagnosed by echocardiography, taken after their BPs were decreased to meet the values of the standard normal. Among them, there were only 41 out of the original 237 patients, 17.3%, who had simple essential hypertension combined with left ventricular hypertrophy without any other co-existing disease. They were the patients selected for this study. All patients were randomly, indiscriminately divided into two groups: one was the control group (Group T), treated with the Telmisartan-based monotherapy; the other was the target group (Group TS), treated with the Telmisartan-based plus simvastatin therapy. The changes of left ventricular hypertrophy and left ventricular function were rediagnosed by echocardiography after 1 year. The results we obtained from this study were as follows: (i) The average BPs at the beginning of the study, of simple essential hypertension combined with left ventricular hypertrophy, were high levels (systolic blood pressure (SBP) 189.21 ± 19.91 mm Hg, diastolic blood pressure 101.40 ± 16.92 mm Hg). (ii) The Telmisartan-based plus simvastatin therapy was significantly effective in lowering the SBP (128.26 ± 9.33 mm Hg vs. 139.22 ± 16.34 mm Hg). (iii) After the 1-year treatment, the parameters of left ventricular hypertrophy in both groups were improved. Compared to group T, there were no differences in the characteristics of the subjects, including interventricular septum, left ventricular mass, left ventricular mass index, ejection fraction, left atrium inner diameter at baseline. The patients' interventricular septum (Group TS 10.30 ± 1.80 mm vs. Group T 10.99 ± 1.68 mm, P < .05), LVM (Group TS 177.43 ± 65.40 g vs. Group T 181.28 ± 65.09 g, P < .05), and LVMI (Group TS 100.97 ± 37.33 g/m(2) vs. Group T 106.54 ± 27.95 g/m(2), P < .05), all dropped more prominently (P < .05) in group TS; the ejection fraction rose more remarkably in group TS (Group TS: 57.50 ± 16.41% to 65.43 ± 11.60%, P < .01 while showing no change in Group T); the left ventricular hypertrophy reversed more significantly and the left ventricular systolic function improved more. (iv) The left atrium inner diameter of Group TS decreased (P < .01), the ratio of E/A, which indicates the left ventricular diastolic function, continued to drop further, showing no change to the trend of left ventricular diastolic function declination. Patients who have hypertension with left ventricular hypertrophy usually suffer other accompanying diseases at the same time. Telmisartan-based plus Simvastatin treatment can significantly reduce SBP, reverse left ventricular hypertrophy, improve the left ventricular systolic function, but it has no effect on reversing the left ventricular diastolic function. This experiment indicated that Simvastatin can reverse left ventricular hypertrophy and improve left systolic function.

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The aim of this study was to examine the function of perivascular adiposa tissue (PVAT) on vascular relaxation response in spontaneously hypertensive rats (SHR) and the modulatory effects of the atorvastatin therapy on the PVAT functions. We investigated the mechanisms of the perivascular adipocyte-derived relaxation factor (PVRF) by using isolated rat's aortic rings and isometric contraction measurements. We found that contraction of the thoracic aorta induced by phenylephrine was significantly attenuated in the presence of PVAT from normotensive Wistar-Kyoto rats (WKY group) or the spontaneously hypertensive rats treated with atorvastatin (SHR-A group, atorvastatin 50mg/kg/day), whereas this effect was not observed in the thoracic aortic rings from the control SHR (SHR group). Transferring the solution incubated with PVAT-intact thoracic aorta to PVAT-free thoracic aorta, it induced a remarkable relaxation response in the WKY but not in the control SHR. Tetraethylammoniumchloride (TEA) could block the above relaxation. It was also shown that the PVRF function was likely, depending on the extracellular [Ca(2+)]; the anti-contractile effect of PVAT could be reduced by the inhibitor of the adenosine triphosphate (ATP)-dependent potassium channels, glibenclamide, and could be reduced by the inhibitor of cyclooxygenase by indomethacin. We thus infer that the PVAT function was distorted in hypertension rats, and the lipid-lowering treatment with atorvastatin could restore the PVAT function. The function of the PVRF may involve the Ca(2+)-activated potassium channels, the ATP-dependent potassium channels in vascular smooth muscle cell (SMC), and the release of PVRF from PVAT may involve prostaglandins (PGs) and the calcium metabolism. These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy.

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OBJECTIVE: Recent studies have shown that perivascular adipose tissue from the rat aorta secretes a substance that can dilate the aorta. The purpose of the present study was to examine whether this vasodilator is also present in human internal thoracic arteries. METHODS: Vascular function of human internal thoracic arteries with and without perivascular adipose tissue was assessed with wire myography, and morphology was examined with light microscopy. RESULTS: The presence of perivascular adipose tissue attenuated the maximal contraction to U 46619 and the contraction to phenylephrine (1 micromol/L) by 37% and 24%, respectively. Transfer of the solution incubated with a perivascular adipose tissue-intact vessel (donor) to a vessel without perivascular adipose tissue (recipient) induced a significant relaxation (36%) in the recipient artery precontracted with phenylephrine. Transfer of incubation solution with perivascular adipose tissue alone also induced a relaxation response in the recipient vessel (37%). The relaxation of the recipient artery induced by the transfer of incubation solution from the donor (artery with intact perivascular adipose tissue or perivascular adipose tissue alone) was absent in vessels precontracted by KCl (60 mmol/L) and was prevented by calcium-dependent potassium channel blockers (tetraethylammonium chloride, 1 mmol/L; iberiotoxin, 100 nmol/L), but not by the voltage-dependent potassium channel blocker 4-aminopyridine (1 mmol/L) and the adenosine triphosphate-dependent potassium channel blocker glibenclamide (10 micromol/L). CONCLUSIONS: Perivascular adipose tissue in human internal thoracic arteries releases a transferable relaxation factor that acts through the activation of calcium-dependent potassium channels. Because perivascular adipose tissue is often removed in coronary artery bypass grafting, retaining perivascular adipose tissue might be helpful in reducing the occurrence of vasospasm of the graft vessels.

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OBJECTIVE: Recent epidemiological studies have shown that there is an increased risk of obesity and hypertension in children born to women who smoked during pregnancy. The aim of this study was to examine the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarette smoke, on postnatal adiposity and blood vessel function. RESEARCH METHODS AND PROCEDURES: Female Wistar rats were given nicotine or saline (vehicle) during pregnancy and lactation. Postnatal growth was determined in the male offspring from weaning until 26 weeks of age. At 26 weeks of age, fat pad weight and the function of the perivascular adipose tissue (PVAT) in the thoracic aorta and mesenteric arteries were examined. RESULTS: Exposure to nicotine resulted in increased postnatal body weight and fat pad weight and an increased amount of PVAT in the offspring. Contraction of the aorta induced by phenylephrine was significantly attenuated in the presence of PVAT, whereas this effect was not observed in the aortic rings from the offspring of nicotine-exposed dams. Phenylephrine-induced contraction without PVAT was not different between saline- and nicotine-exposed rats. Transfer of solution incubated with PVAT-intact aorta to PVAT-free aorta induced a marked relaxation response in the rats from saline-exposed dams, but this relaxation response was significantly impaired in the rats from nicotine-exposed dams. DISCUSSION: Our results showed that prenatal nicotine exposure increased adiposity and caused an alteration in the modulatory function of PVAT on vascular relaxation response, thus providing insight into the mechanisms underlying the increased prevalence of obesity and hypertension in children exposed to cigarette smoke in utero.

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The purpose of this study was to investigate the role of the renin-angiotensin-aldosterone system in hypertension development and cardiovascular structural changes in a salt-sensitive hypertensive model induced by capsaicin (CAP). Newborn male Wistar rats were injected with either capsaicin or vehicle. After weaning at 3 weeks, these rats were divided into the following six treatment groups: capsaicin plus high-salt diet (CAP+HS), control plus high-salt diet (CON+HS), control plus normal salt diet (CON+NS), capsaicin plus high-salt diet and telmisartan (CAP+HS+T, 10 mg/kg/day), capsaicin plus high-salt diet and perindopril (CAP+HS+P, 2 mg/kg/day), and capsaicin plus high-salt diet and spironolactone (CAP+HS+S, 80 mg/kg/day). Treatment with different salt diets and drugs was initiated at 3 weeks of age and lasted 18 weeks. We found that beginning at the second week after the initiation of the treatment, blood pressure became significantly higher in CAP+HS than in other groups, accompanied by the development of cardiac hypertrophy. Treatment with telmisartan, perindopril or spironolactone prevented the development of hypertension in the CAP+HS group. Cardiac hypertrophy was prevented in the perindopril treatment group. The medial thickness, media-to-lumen ratio and cross-sectional area of the thoracic, renal and mesenteric arteries were significantly increased in CAP+HS than in other groups. Lumen diameter was similar in all the vessels among all the groups. Treatment with telmisartan, perindopril or spironolactone prevented the development of vascular remodeling, as found in the CAP+HS group. Beginning at 8 weeks after the initiation of the salt diet treatment (11 weeks of age), blood pressure also became higher in CON+HS than in CON+NS, but lower than CAP+HS. Structural changes of vessels were also present in CON+HS, but the degree of change was less when compared with CAP+HS. We conclude that neonatal treatment with capsaicin plus a high-salt diet, and a high-salt diet alone both induced hypertension development in normal Wistar rats, which are associated with cardiovascular remodeling. The renin-angiotensin-aldosterone system is involved in this salt-sensitive model because treatment that interfered with this system also prevented the development of hypertension and vascular remodeling.

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1. The objective of the present study was to investigate the arterial structural changes in a salt-sensitive hypertensive rat model induced by treatment with capsaicin. 2. Newborn male Wistar rats were treated with 50 mg/kg capsaicin subcutaneously for 2 days. Control rats were treated with vehicle solution (5% ethanol and 5% Tween 80 in saline). After weaning at 3 weeks, rats were divided into four groups: (i) control with a normal salt diet (0.5% NaCl; CON + NS); (ii) control with a high-salt diet (4% NaCl; CON + HS); (iii) capsaicin plus normal salt diet (CAP + NS); and (iv) capsaicin plus a high-salt diet (CAP + HS). Treatment with different salt diets was initiated at 3 weeks of age and lasted for 18 weeks. Tail-cuff systolic blood pressure (BP) and bodyweight were examined. At the end of the treatment period, blood vessels were prepared by perfusion fixation. Heart weight and vascular dimensions were measured in the thoracic (artery) aorta, renal artery and mesenteric artery. 3. Two weeks after the initiation of the salt diet treatment, BP became significantly higher in the CAP + HS group than in any of the other groups and this difference was maintained until the end of the treatment period. 4. Beginning at 8 weeks after the initiation of the salt diet treatment (11 weeks of age), BP became higher in the CON + HS group than in the CON + NS and CAP + NS groups. Blood pressure was not significantly different between the CON + NS and CAP + NS groups. 5. Media thickness, media thickness to lumen ratio and cross-sectional area of the aorta, renal artery and mesenteric artery were significantly increased in the CAP + HS group compared with the other groups. Heart weight was also increased in the CAP + HS and CON + HS groups compared with the other groups. 6. Similar structural changes in the blood vessels and heart were also found in the CON + HS group compared with the CON + NS group. Lumen diameter was not altered by the treatments in any of the arteries studied. 7. We conclude that treatment with capsaicin increased the sensitivity of the BP of these rats to salt and this increase in BP is correlated with hypertrophy of the arteries (vascular remodelling) with no change in lumen size. A long-term high-sodium load induced hypertension in normal Wistar rats, which was accompanied by cardiovascular hypertrophy.

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