Effects of Aspirin on Pregnancy Outcome and Serum Endothelin-1 and Thrombomodulin Levels in Pregnancy Patients with Chronic Hypertension

Objective: To investigate the effect of aspirin on pregnancy outcome and serum levels of endothelin-1 (ET-1) and thrombomodulin (TM) in pregnancy patients with chronic hypertension. Methods: Selected patients with chronic hypertension (mild to moderate) during pregnancy, who were enrolled and delivered in the Beijing Tongren Hospital Department of Obstetrics and Gynecology between January 1, 2019 and December 30, 2020. The patients were randomly divided into control group (60) and experimental group (60). The control group was treated with labetalol and the test group was treated with labetalol and aspirin. The therapeutic effect and pregnancy outcome of the two groups were compared. The serum levels of ET-1 and TM were measured before treatment and one week after treatment. Results: Systolic blood pressure (SBP) decreased significantly one week after treatment in the two groups (P < 0.05). One week after treatment, the values of ET-1 and TM in the experimental group were significantly lower than those in the Control Group, the difference is statistically significant (P < 0.05). The incidence of Preeclampsia, intrauterine growth retardation, oligohydramnios, placental abruption, Cesarean section and preterm birth in the experimental group was significantly lower than that in the control group. There was significant difference between the two groups, especially Preeclampsia and Intrauterine Growth Retardation (P < 0.05). Conclusion: Besides routine treatment, aspirin can improve the outcome of pregnant women with chronic hypertension, which may be related to the regulation of ET-1 and TM by aspirin.

Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Neuroprotective effect of mesenchymal stem cellderived extracellular vesicles on optic nerve injury in chronic ocular hypertension

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.

Expression of Nogo-A on the retina in rat model with chronic ocular hypertension

AIMTo study the expressive variation of Nogo-A on rat retina in the process of chronic ocular hypertension.

TGF-β_1 in retinal ganglion cells in rats with chronic ocular hypertension: its expression and anti-apoptotic effect

AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the immunohistochemiscal S-P method and real-time PCR in the normally control group, the ocular hypertension group (experimental group A), the ocular hypertension plus antibody intervention group (experimental group B) and the ocular hypertension plus antigen intervention group (experimental group C) at 1, 2, 3 and 4 weeks postoperatively. The count of apoptotic RCGs was measured using the TUNEL method. RESULTS: The expression of TGF-β1 was significantly higher in experimental group C than that in other three groups (P<0.05). The expression was the lowest in experimental group B (4.17%). A statistically significant difference was noted between the four groups (P <0.01). The count of apoptotic RCGs was statistically significantly lower in experimental group C than that in the experimental groups A and B (P <0.01). A statistically significant difference was noted in the count of apoptotic RCGs between these three experimental groups (P <0.01). CONCLUSION: TGF-β1 can inhibit the apoptosis of RCGs in rats with chronic ocular hypertension.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension:State of the art

Chronic thromboembolic pulmonary hypertension(CTEPH)is a complex chronic disease in which pulmonary artery stenosis or obstruction caused by organized thrombus can lead to increased pulmonary artery pressure and pulmonary vascular resistance,ultimately triggering progressive right heart failure and death.Currently,its exact mechanism is not fully understood.Pulmonary endarterectomy(PEA)has immediate effects with low perioperative mortality and satisfactory prognosis in experienced expert centers for CTEPH patients with proximal lesions.Nevertheless,37%of patients are deemed unsuitable for PEA surgery due to comorbidities and other factors,and nearly half of the operated patients have residual or recurrent pulmonary hypertension.Riociguat is the only approved drug for CTEPH,although its effect is limited.Balloon pulmonary angioplasty(BPA)is a promising alternative treatment for patients with CTEPH.After more than 30 years of development and refinements,emerging evidence has confirmed its role in patients with inoperable CTEPH or residual/recurrent pulmonary hypertension,with acceptable complications and comparable longterm prognosis to PEA.This review summarizes the pathophysiology of CTEPH,BPA history and development,therapeutic principles,indications and contraindications,interventional procedures,imaging modalities,efficacy and prognosis,complications and management,bridging and hybrid therapies,ongoing clinical trials and future prospects.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

L-and T-type Ca^(2+)channels dichotomously contribute to retinal ganglion cell injury in experimental glaucoma

Retinal ganglion cell apoptotic death is the main pathological characteristic of glaucoma,which is the leading cause of irreversible blindness.Disruption of Ca^(2+)homeostasis plays an important role in glaucoma.Voltage-gated Ca^(2+)channel blockers have been shown to improve vision in patients with glaucoma.However,whether and how voltage-gated Ca^(2+)channels are involved in retinal ganglion cell apoptotic death are largely unknown.In this study,we found that total Ca^(2+)current densities in retinal ganglion cells were reduced in a rat model of chronic ocular hypertension experimental glaucoma,as determined by whole-cell patch-clamp electrophysiological recordings.Further analysis showed that L-type Ca^(2+)currents were downregulated while T-type Ca^(2+)currents were upregulated at the later stage of glaucoma.Western blot assay and immunofluorescence experiments confirmed that expression of the Ca_(V)1.2 subunit of L-type Ca^(2+)channels was reduced and expression of the Ca_(V)3.3 subunit of T-type Ca^(2+)channels was increased in retinas of the chronic ocular hypertension model.Soluble tumor necrosis factor-α,an important inflammatory factor,inhibited the L-type Ca^(2+)current of isolated retinal ganglion cells from control rats and enhanced the T-type Ca^(2+)current.These changes were blocked by the tumor necrosis factor-αinhibitor XPro1595,indicating that both types of Ca^(2+)currents may be mediated by soluble tumor necrosis factor-α.The intracellular mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and nuclear factor kappa-B signaling pathway mediate the effects of tumor necrosis factor-α.TUNEL assays revealed that mibefradil,a T-type calcium channel blocker,reduced the number of apoptotic retinal ganglion cells in the rat model of chronic ocular hypertension.These results suggest that T-type Ca^(2+)channels are involved in disrupted Ca^(2+)homeostasis and apoptosis of retinal ganglion cells in glaucoma,and application of T-type Ca^(2+)channel blockers,especially a specific CaV3.3 blocker,may be a potential strategy for the treatment of glaucoma.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension： preliminary exploration in China

Background Pulmonary endarterectomy is safe and effective surgical treatment for chronic thromboembolic pulmonary hypertension. This study aimed to evaluate the efficacy of pulmonary endarterectomy in treatment of thromboembolic pulmonary hypertension. Methods A retrospective study of 15 patients who underwent pulmonary endarterectomy in Beijing Chaoyang Hospital was performed. Obvious pulmonary hypertension and hypoxemia were observed in all patients. Bilateral pulmonary endarterectomy was performed under cardiopulmonary bypass with profound hypothermic circulatory arrest. Results Two patients （2/15） died of residual postoperative pulmonary hypertension and bleeding complication. The other 13 cases had significant decrease in systolic pulmonary artery pressure （（92.8＋_27.4） mmHg vs. （49.3＋18.6） mmHg） and pulmonary vascular resistance （（938.7±464.1） dynes.s.cm5 vs. （316.8±153.3） dynes＇s.cm5）, great improvement in cardiac index （（2.31：LK）.69） L.min-l.m2 vs. （3.85±1.21） L.min-l.m2）, arterial oxygen saturation （0.67±O.11 vs. 0.96±0.22） and mixed venous 02 saturation （0.52±0.12 vs. 0.74±0.16） postoperatively compared to preoperative data. Mid-term follow-up showed that the cardiac function of all cases returned to NYHA class I or II, with great improvement in 6-minute walking distance （（138±36） m） and quality of life. Conclusions Bilateral pulmonary endarterectomy using cardiopulmonary bypass with the aid of deep hypothermia and circulatory arrest can effectively reduce pulmonary hypertension and provide good mid-term hemodynamic and symptomatic results with low surgical mortality rate and few complications.

Serum Bilirubin and 6-min Walk Distance as Prognostic Predictors for Inoperable Chronic Thromboembolic Pulmonary Hypertension： A Prospective Cohort Study

Background： Inoperable chronic thromboembolic pulmonary hypertension （CTEPH） is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers （such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]） combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. Methods： From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance （6MWD） results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. Results： During the follow-up, 22 patients （29%） died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin （hazard ratio [HR] = 7.755, P 〈 0.001）, elevated N-terminal of the prohormone brain natriuretic peptide （HR = 1.001, P = 0.001）, decreased 6MWD （HR = 0.990, P 〈 0.001）, increased central venous pressure （HR = 1.074, P = 0.040）, and higher pulmonary vascular resistance （HR = 1.001, P = 0.018） were associated with an increased risk of mortality. Serum concentrations of total bilirubin （HR = 4.755, P = 0.007） and 6MWD （HR = 0.994, P = 0.017） were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia （≥23.7 μmol/L） had markedly worse survival than those with normobilirubinemia. Conclusion： Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.

A male with chronic thromboembolic pulmonary hypertension caused by isolated noncompaction of ventricular myocardium

Noncompaction of the ventricular myocardium （NVM） is a rare disease of endomyocardialmorphogenesis characterized by numerous, prominent trabeculations and deep intertrabecular recesses. It is commonly associated with congenital heart disease. Isolated noncompaction of the ventricular myocardium （INVM） is thought to be caused by arrest of normal embryogenesis of the endocardium and myocardimn. A significant amount of data on INVM are available for the left ventricle but right ventricular involvement is rare.

A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection

This study aimed to modify a chronic ocular hypertension(OHT)rat model to screen for potential compounds to protect retinal ganglion cells(RGCs)from responding to increased intraocular pressure(IOP).A total of 266 rats were prepared and randomly grouped according to different time-points,namely,weeks 3,8,16,and 24.Rats were sedated and eye examination was performed to score as the corneal damage on a scale of 1 to 4.The OHT rat model was created via the injection of a hypertonic saline solution into the episcleral veins once weekly for two weeks.OHT was identified when the IOP at week 0 was≥6 mmHg than that at week-2 for the same eye.Viable RGCs were labeled by injecting 4%FluoroGold.Rats were sacrificed,and the eyes were enucleated and fixed.The fixed retinas were dissected to prepare flat whole-mounts.The viable RGCs were visualized and imaged.The IOP(meanβ±βSD)was calculated,and data were analyzed by the paired t-test and one-way ANOVA.The OHT model was created in 234 of 266 rats(87.97%),whereas 32 rats(12.03%)were removed from the study because of the absence of IOP elevation(11.28%)and/or corneal damage scores over 4(0.75%).IOP was elevated by as much as 81.35%for 24 weeks.The average IOP was(16.68β±β0.98)βmmHg in non-OHT eyes(n=234),but was(27.95±0.97)βmmHg in OHT eyes(n=234).Viable RGCs in the OHT eyes were significantly decreased in a time-dependent manner by 29.41%,38.24%,55.32%,and 59.30%at weeks 3,8,16,and 24,respectively,as compared to viable RGCs in the non-OHT eyes(P<β0.05).The OHT model was successfully created in 88%of the rats.The IOP in the OHT eyes was elevated by approximately 81%for 24 weeks.The number of viable RGCs was decreased by 59%of the rats in a time-dependent manner.The modified OHT model may provide an effective and reliable method for screening drugs to protect RGCs from glaucoma.

STATUS AND CONTROL POLICY OF MAIN CHRONIC DISEASES IN COMMUNITY HEALTH MANAGEMENT BASES IN SHANGHAI AND GUANGDONG

Objective To investigate the current conditions of the main chronic diseases and to make the control policy in community health management base in China. MethodsThe questionnaire consisting of prevalence, awareness rate, management rate, behavior correct rate, control rate, and medicine obey was used to survey the chronic disease condition in 2009. A total of 809 736 residents were randomly selected from Shanghai and Guangdong, China. ResultsThe hypertension prevalence was 17.81%. From sex analysis, the female has higher rate than male in hypertension prevalence, understand rate, management rate, behavior correct rate, control rate, and medicine obey rate. From age analysis, the prevalence, understand rate, management rate, control rate, and medicine obey were increasing along with the age, but behavior correct rate was not in this condition. The diabetes prevalence was 6.92%. To compare with Shanghai and Guangzhou in 5 aspects, the prevalence of chronic diseases was alike. Except lower behavior correct rate in Shanghai, management rate, behavior correct rate, control rate, and medicine obey rate were higher in Shanghai. ConclusionThe government must take main principle in chronic disease control. Base construction of community health management and increase management level of chronic diseases should be enhanced and practitioner's knowledge of chronic disease management should also be enhanced.

Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure

Background Pulmonary thromboendarterectomy （PTE） has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension （CTEPH）. This study aimed to characterize if pulmonary oligemia maneuver （POM） can alleviate pulmonary artery injury during PTE procedure. Methods A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure. They were retrospectively classified as non-POM group （group A, n=55） or POM group （group B, n=57）. Members from group B received POM during rewarming period, whereas members from group A did not. Results There were three （5.45%） early deaths in group A, no death in group B （0） （Fisher＇s exact test, P=0.118）. Six patients in group A needed extracorporeal membrane oxygenation （ECMO） as life support after the PTE procedure, no patients in group B needed ECMO （Fisher＇s exact test, P=0.013）. The patients in group B had a shorter intubation and ICU stay, lower mean pulmonary arterial pressure （mPAP） and pulmonary vascular resistance （PVR）, higher partial pressure of oxygen in artery （PaO2） and arterial oxygen saturation （SaO2） and less medical expenditure than patients in group A. With a mean follow-up time of （58.3 ± 30.6） months, two patients in group A and one patient in group B died. The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance. Three months post the PTE procedure, the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance （P=0.393）. Conclusion POM can alleviate pulmonary artery injury, shorten ICU stay and intubation time, and lower down the rate of ECMO after PTE procedure.

P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice

Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.

Pulmonary artery injury management during pulmonary thromboendarterectomy

Pulmonary thromboendarterectomy （PEA） is the recommended treatment for chronic thromboembolic pulmonary hypertension （CTEPH）.1 Pulmonary artery injury is a major risk factor during PEA performed at less experienced surgical centers and is associated with adverse short-term consequences.In-hospital mortality may be as high as 15% in some PEA case series,with pulmonary artery injury and persistent pulmonary hypertension as the principal etiologies.2 Many techniques have been used to prevent pulmonary artery injury during PEA,but once the injury occurs,the prognosis is poor and may even result in death.Out of 202 PEA procedures performed at our surgical center,we successfully managed two cases of severe pulmonary artery injury and report our experience in the present case series.Keywords：chronic thromboembolic pulmonary hypertension; pulmonary thromboendarterectomy; pulmonary artery injury