Does ambient air quality standard contribute to green innovation of enterprises in China? Implications for environmental protection and public health.

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Follow-up care delivery in community-based hypertension and type 2 diabetes management: a multi-centre, survey study among rural primary care physicians in China.

BACKGROUND: Follow-up care is crucial but challenging for disease management particularly in rural areas with limited healthcare resources and clinical capacity, yet few studies have been conducted from the perspective of rural primary care physicians (PCPs). We assessed the frequency of follow-up care delivered by rural PCPs for hypertension and type 2 diabetes - the two most common long-term conditions. METHODS: We conducted a multi-centre, self-administered survey study built upon existing general practice course programmes for rural PCPs in four provinces. Information on follow-up care delivery were collected from rural PCPs attending centralised in-class teaching sessions using a set of close-ended, multiple choice questions. Binary logistic regression analysis was performed to examine physician-level factors associated with non-attainment of the target frequency of follow-up care for hypertension and type 2 diabetes, respectively. The final sample consisted of rural PCPs from 52 township-level regions. The Complex Samples module was used in the statistical analysis to account for the multistage sample design. RESULTS: The overall response rate was 91.4%. Around one fifth of PCPs in rural practices did not achieve the target frequency of follow-up care delivery (18.7% for hypertension; 21.6% for type 2 diabetes). Higher education level of physicians, increased volume of daily patients seen, and no provision of home visits were risk factors for non-attainment of the target frequency of follow-up care for both conditions. Moreover, village physicians with less working experiences tended to have less frequent follow-up care delivery in type 2 diabetes management. CONCLUSIONS: Efforts that are solely devoted to enhancing rural physicians' education may not directly translate into strong motivation and active commitment to service provision given the possible existence of clinical inertia and workload-related factors. Risk factors identified for target non-attainment in the follow-up care delivery may provide areas for capacity building programmes in rural primary care practice.

Cyanidin ameliorates cisplatin-induced cardiotoxicity via inhibition of ROS-mediated apoptosis.

Oxidative stress and apoptosis serve an essential role in cisplatin-induced cardiotoxicity, which limits its clinical use, and increases the risk of cardiovascular disease. As a natural drug, the antioxidant and antitumor effects of cyanidin have been recognized, but its protective effect on cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with cisplatin (1-40 µM) in the presence or absence of cyanidin (40-80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that cyanidin was able to dose-dependently reverse cisplatin-induced cell damage and apoptosis, attenuate the accumulation of reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of caspase 3, caspase 9, but not caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in cisplatin-induced apoptosis. Cyanidin was able to block the translocation of Bax and reduce the release of cytochrome c from cytoplasm. These data indicate that cyanidin attenuates cisplatin-induced cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated kinase signaling pathways may also serve important roles.

Cordycepin inhibits vascular adhesion molecule expression in TNF-α-stimulated vascular muscle cells.

Atherosclerosis is a chronic inflammatory disease, which is associated with the increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Cordycepin is one of the major bioactive components of Ophiocordyceps sinensis that has been demonstrated to exert anti-atherogenic activity; however, its molecular mechanisms are poorly understood. The aim of the present study was to examine the in vitro effects of cordycepin on the tumor necrosis factor (TNF)-α-induced suppression of adhesion molecule expression. The results of the present study demonstrated that cordycepin markedly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in TNF-α-stimulated human aortic vascular smooth muscle cells (HA-VSMCs). Cordycepin significantly inhibited the TNF-α-induced mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) activation (P<0.05), markedly inhibited the TNF-α-induced expression level of nuclear factor (NF)-κB p65 and markedly prevented the TNF-α-associated degradation of IκBα in HA-VSMCs. The results of the present study suggest that cordycepin inhibits the expression of VCAM-1 and ICAM-1 in TNF-α-stimulated HA-VSMCs via downregulating the MAPK/Akt/NF-κB signaling pathway. Therefore, cordycepin may have a potential therapeutic application for preventing the advancement of atherosclerotic lesions.

Myricitrin inhibits vascular adhesion molecule expression in TNF­α­stimulated vascular smooth muscle cells.

Increased expression of adhesion molecules is thought to serve an important role in the pathogenesis of atherosclerosis. Myricitrin, a bioactive compound of Myrica cerifera, has been demonstrated to exhibit anti­atherogenic effects. However, the effect of myricitrin on the expression of adhesion molecules in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, the aim of the present study was to evaluate the inhibitory effects of myricitrin on tumor necrosis factor­α (TNF­α)­induced expression of adhesion molecules in VSMCs in vitro. The results revealed that myricitrin inhibited the adhesion of human THP­1 monocyte cells to TNF­α­stimulated mouse MOVAS­1 VSMC cells, and reduced the expression of adhesion molecules in TNF­α­stimulated MOVAS­1 cells. In addition, myricitrin significantly inhibited the TNF­α­induced expression of nuclear factor (NF)­κB p65, and prevented the TNF­α­induced degradation of nuclear factor of κ light chain enhancer in B­cells inhibitor α. Furthermore, myricitrin inhibited the production of intracellular reactive oxygen species in TNF­α­stimulated MOVAS­1 cells. In conclusion, the results of the present study indicated that myricitrin inhibits the expression of vascular cell adhesion protein­1 and intercellular adhesion molecule­1 in TNF­α­stimulated MOVAS­1 cells potentially via the NF­κB signaling pathway. Therefore, myricitrin may be an effective pharmacological agent for the prevention or treatment of atherosclerosis.

CHADS2 and CHA2DS2-VASc Scores Predict the Risk of Ischemic Stroke Outcome in Patients with Interatrial Block without Atrial Fibrillation.

AIM: To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF). METHODS: A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63±10 years) with IAB and without AF. IAB was defined as P-wave duration ＞120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA. RESULTS: During the mean follow-up period of 4.9±0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P＜0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥3 (sensitivity=0.455 and specificity=0.747) and a CHA2DS2-VASc score ≥4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203-1.677; P＜0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins. CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.

Usefulness of a Combination of Interatrial Block and a High CHADS2 Score to Predict New Onset Atrial Fibrillation.

Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.

Advanced interatrial block predicts clinical recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: It has been demonstrated that advanced interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF); however, the impact of advanced IAB on recurrence of paroxysmal AF after catheter ablation is not clear. METHODS: 204 consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein (PV) isolation were prospectively enrolled. In all patients, a resting electrocardiogram in sinus rhythm was evaluated for the presence of advanced IAB, defined as a P-wave duration >120ms and biphasic (±) morphology in the inferior leads. Advanced IAB was detected in 20.1% of patients. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30s beyond 3 months after the catheter ablation in the absence of any antiarrhythmic treatment. RESULTS: During the mean follow-up period of 13.9±6.2 months (range, 3-27 months), 62 patients (30.4%) developed recurrence of AF. The recurrence rate was higher in patients with advanced IAB than those without advanced IAB (46.3% vs. 26.4%, p=0.006). Cox regression analysis with adjustment for age, P-wave duration, CHADS2 score, and PV isolation identified advanced IAB (hazard ratio, 2.111; 95% confidence interval, 1.034-4.308; p=0.040) and left atrial diameter (hazard ratio, 1.051; 95% confidence interval, 1.004-1.100; p=0.034) as two independent predictors of recurrence of AF. CONCLUSIONS: Patients with advanced IAB were at an increased risk of AF recurrence after catheter ablation.

Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

[Killing effect of garlic extract on Schistosoma japonicum cercariae and Oncomelania snails].

The killing effect of different concentrations of garlic extract solution on Schistosoma japonicum cercariae and Oncomelania snails was observed under dissecting microscope. Mice were infected by cercariae through the abdominal skin daubed by garlic solution or by deionized water as control. The results showed that the cercariae were killed in (77.33 +/- 25.01) s in average, it needed (73.00 +/- 1.73)- (299.67 +/- 18.96) s under the garlic solution concentrations of 50.00%-0.79% respectively, while the cercariae kept alive in 600 s in the control. The snails were killed in 1 d by 100% garlic solution but no death in the control in 2 d. No mouse daubed with different concentrations of garlic solution was found infected by schistosomes while 100% of the control mice got infected. It is concluded that the garlic shows satisfactory effect in killing cercariae and Oncomelania snails, and may prevent schistosome infection by daubing the skin.

Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure.

BACKGROUND: Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF). Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction. METHODS: Sixty adult rats underwent sham or coronary ligation to induce HF. Four weeks after ligation, 29 animals with LV ejective fraction ≤ 50% were randomized to receive either vehicle or rhNRG-1 (10 µg×kg(-1)×d(-1), I.V.) for 10 days, another 12 sham-operated animals were given no treatment. Echocardiography was used to determine physiological changes. Mitochondrial membrane potential (MMP), respiratory function and tissue adenosine triphosphate (ATP) production were analyzed. Cytochrome c expression and cardiomyocyte apoptosis were determined. Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR. RESULTS: Compared with sham-operated animals, vehicle treated HF rats exhibited severe LV remodeling and dysfunction, significant mitochondrial dysfunction, increased mitochondrial cytochrome c release, increased myocyte apoptosis and enhanced oxidative stress. Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function. Concomitant with this change, mitochondrial dysfunction was significantly attenuated; with ATP production, MMP and respiratory function restored, cytochrome c release and apoptosis inhibited, and oxidative stress reduced. CONCLUSION: The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart, this beneficial effect is related to reducing mitochondrial dysfunction, myocyte apoptosis and oxidative stress.

Factors influencing recovery of left ventricular structure in patients with chronic heart failure.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and ß-blockers (ßB) have beneficial effects on left ventricular (LV) remodeling, alleviate symptoms and reduce morbidity and mortality in patients with chronic heart failure (CHF). However the correlation between the d osages of ACE inhibitors, ßB, and recovery of LV structure remains controversial. Clinical factors associated with recovery of normal ventricular structure in CHF patients receiving medical therapy are poorly defined. Here we aimed to identify variables associated with recovery of normal or near-normal structure in patients with CHF. METHODS: We recruited 231 consecutive CHF outpatients, left ventricular ejection fraction (LVEF) ≤ 40% and left ventricular end diastolic diameter (LVEDD) > 55/50 mm (male/female), who were receiving optimal pharmacotherapy between January 2001 and June 2009, and followed them until December 31, 2009. They were divided into three groups according to LVEDD and whether they were still alive at final follow-up: group A, LVEDD ≤ 60/55 mm (male/female); group B, LVEDD > 60/55 mm (male/female); and group C, those who died before final follow-up. Apart from group C, univariate analysis was performed followed by Logistic multivariate analysis to determine the predictors of recovery of LV structure. RESULTS: A total of 217 patients completed follow-up, and median follow-up time was 35 months (range 6 - 108). Twenty-five patients died during that period; the all-cause mortality rate was 11.5%. Group A showed clinical characteristics as follows: the shortest duration of disease and shortest QRS width, the lowest N-terminal brain natriuretic peptide (NT-proBNP) at baseline, the highest dose of ßB usage, the highest systolic blood pressure (SBP), diastolic blood pressure (DBP) and the lowest New York Heart Association (NYHA) classification, serum creatinine, uric acid, total bilirubin and NT-proBNP after treatment. Logistic multivariate analysis was performed according to recovery or no recovery of LV structure. Data showed that LVEF at follow-up (P = 0.013), mitral regurgitation at baseline (P = 0.020), LVEDD at baseline (P = 0.031), and ßB dosage (P = 0.041) were independently associated with recovery of LV diameter. CONCLUSION: Our study suggests that four clinical variables may predict recovery of LV structure to normal or near-normal values with optimal drug therapy alone, and may be used to discriminate between patients who should receive optimal pharmacotherapy and those who require more aggressive therapeutic interventions.

[Optimal pharmacotherapy according to guideline improved prognosis of outpatients with chronic heart failure].

OBJECTIVE: To evaluate the effects of optimal pharmacotherapy according to guideline on treating chronic heart failure(CHF) in real world clinical practice. METHODS: A total of 231 consecutive outpatients with reduced left ventricular ejection fraction (LVEF ≤ 40%) and enlarged left ventricular end diastolic diameter (male > 55 mm, female > 60 mm) were recruited from January 2001 to June 2009. All patients were treated with optimal pharmacotherapy according to guideline recommendations and followed up to December 31, 2009. Mortality, rehospitalization and changes of heart size and cardiac function at baseline and at the end of follow-up period were analyzed. RESULTS: (1) 14 patients were lost during follow-up (6.1%), and follow-up was complete in 217 patients (93.9%). 97.2% and 98.2% patients were prescribed angiotensin converting enzyme (ACE) inhibitors and ß-blockers (ßB). Combined of ACE inhibitors and BB use was applied in 95.3% patients. The target dose of ACE inhibitors and ßB were reached in 50.7% and 37.3% patients. (2) Lower mortality and re-hospitalization rates were observed in this cohort: all-cause morality, average annual mortality was 11.5% and 3.9% respectively. Re-hospitalization rate was 27.6%. (3) Left ventricular end-diastolic diameter (LVEDD) decreased from (68.2 ± 7.2) mm to (62.2 ± 9.6) mm. LVEDD value was normal or near normal (male ≤ 60 mm, female ≤ 55 mm) in 43.2% patients. LVEF improved form (29.8 ± 7.5)% to (43.3 ± 11.8)%, LVEF was > 40% in 60.4% patients, LVEF was ≤ 40% but increased ≥ 10% after treatment in 22.9% patients. CONCLUSION: Optimal pharmacotherapy according to guideline can improve prognosis of outpatients with CHF.

[Effects of glucagon on plasma ghrelin level in type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glucagon on ghrelin secretion in type 2 diabetes mellitus (T2DM) patients. METHODS: Circulating ghrelin and C-peptide were measured during glucagon stimulation test in 38 cases with T2DM and 30 cases in normal controls (NC) at the 1st Affiliated Hospital of Shantou University from May 2006 to December 2007. RESULTS: (1) There was no significant difference in the fasting C-peptide and fasting ghrelin levels of the NC group were (1.3 +/- 0.6) microg/L and (3.0 +/- 1.0) ng/ml respectively, both not significantly different from those of the T2DM group [(1.2 +/- 0.4) microg/L and (2.7 +/- 0.8) microg/L respectively, P > 0.05 and P > 0.05]; six minutes after the injection of glucagon, the C-peptide level of the T2DM group increased to (2.0 +/- 0.8) microg/L (P < 0.01), and that of the NC group increased to (3.0 +/- 0.8) microg/L (P < 0.01), and the C-peptide level 6 min after of the T2DM group was significantly lower than that of the NC group (P < 0.01). The ghrelin level 6 min after the injection of glucagon of the NC group was (2.3 +/- 0.7) microg/L, significantly lower than that before the injection (P < 0.01). But the ghrelin level 6 min after the injection of glucagon of the T2DM group was (2.9 +/- 0.9) microg/L, NOT significantly different from that before the injection (P > 0.05). (2) Fasting ghrelin level was significantly negatively correlated with the waist circumference (r = -0.343, P < 0.05). CONCLUSION: In healthy subjects exogenous glucagon decreases the ghrelin level. Ghrelin may be associated with the beta-cell hypofunction and first-phase insulin secretion defects in T2DM. Insulin, glucagon, and ghrelin secreted influence each other to regulate glucose homeostasis.