Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

El papel de la Ivabradina y la titulación de los betabloqueadores en la insuficiencia cardíaca: una serie de casos y revisión de la literatura / The role of Ivabradine and beta-blocker titration in heart failure: a case series and literature review

RESUMEN Introducción y objetivos : La insuficiencia cardíaca (IC) es una preocupación creciente de salud pública. Si bien los betabloqueantes (BB) son la base del tratamiento, lograr reducciones objetivo de frecuencia cardíaca puede ser difícil debido a los efectos secundarios y la tolerancia limitada. La ivabradina, un inhibidor único de la corriente If, ofrece un enfoque complementario para controlar la frecuencia cardíaca sin afectar la contractilidad. El objetivo de este estudio fue evaluar la eficacia de agregar ivabradina a la terapia BB en pacientes con IC. Métodos: Se realizó un estudio observacional retrospectivo en un hospital privado en San José, Costa Rica se analizaron 7 casos de pacientes tratados con BB a los cuales posteriormente se les adicionó ivabradina. Se recopilaron datos demo- gráficos, las características clínicas, la frecuencia cardíaca previa y posterior a la ivabradina, la clase funcional NYHA y los valores de laboratorio seleccionados. Resultados: La ivabradina redujo significativamente la frecuencia cardíaca en reposo en un promedio de 26,87 latidos por minuto. El 42,86% alcanzó la dosis meta de su BB inicial después de agregar ivabradina. La clase funcional NYHA se mantuvo estable o mejoró en todos los casos. Conclusiones: Estos resultados sugieren que agregar ivabradina a la terapia BB puede ser una estrategia eficaz para optimizar el control de la frecuencia cardíaca en pacientes con IC. Este enfoque puede mejorar la tolerabilidad de BB, lo que lleva a un mayor manejo de la dosis meta y posiblemente mejores resultados clínicos.

ABSTRACT Introduction and objectives: Heart failure (HF) is a growing public health concern. While beta-blockers (BBs) are the cornerstone of treatment, achieving target heart rate reductions can be difficult due to side effects and limited tolerance. Ivabradine, a unique inhibitor of the If current, offers a complementary approach to controlling heart rate without affecting contractility. This study aimed to evaluate the effectiveness of adding ivabradine to BB therapy in patients with HF. Methods : A retrospective observational study was conducted at a private hospital in San José, Costa Rica. Seven cases of patients treated with BBs who were subsequently added to ivabradine were analyzed. Demographic data, clinical characteristics, heart rate before and after ivabradine, NYHA functional class, and selected laboratory values were collected. Results : Ivabradine significantly reduced resting heart rate by an average of 26.87 beats per minute. Forty-two-point eight-six percent (42.86%) achieved the target dose of their initial BB after adding ivabradine. NYHA functional class remained stable or improved in all cases. Conclusions: These results suggest that adding ivabradine to BB therapy may be an effective strategy to optimize heart rate control in patients with HF. This approach may improve BB tolerability, leading to greater target dose management and possibly better clinical outcomes.

Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients. Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial. Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 & 60, patients achieving target BP (<140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported. Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58?mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm?Hg. The upper boundary of the 95% CI was below the margin of 10?mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days. Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Clinical advantages of nebivolol in the treatment of hypertension / 中国药房

β-blocker is one of the commonly used anti-hypertensive drugs， and there are obvious differences in the selection of this class of drugs. Nebivolol is a third-generation β-blocker with a unique mechanism of action. This article summarizes the clinical application of nebivolol in anti-hypertensive treatment in recent years， and it is found that compared with other β-blockers， nebivolol has certain clinical treatment advantages. In addition to having a significant antihypertensive effect， it also has little impact on sexual function and heart rate of patients， and does not affect the blood glucose and lipid metabolism， so the drug is more suitable for some special groups of patients， including sexually active male hypertensive patients， hypertensive patients with complications such as type 2 diabetes mellitus and metabolic syndrome.

Tumor perfusion enhancement effect combined with programmed cell death-Ligand 1 antibody improves the immune microenvironment of solid tumors / 中华超声影像学杂志

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Application of video laryngoscope combined with bronchial blocker and double-lumen tube in the standardized training of anesthesia for tracheal intubation / 中华医学教育探索杂志

Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.

Promoting effect of AGTR1 blocker olmesartan on the apoptosis of HTF and its mechanism / 中华实验眼科杂志

Objective:To study the effect and mechanism of angiotensin type 1 receptor (AGTR1) blocker olmesartan (OMS) on the apoptosis of human Tenon capsule fibroblasts (HTF).Methods:Tenon capsule tissues were obtained from patients during strabismus surgery in the Second Affiliated Hospital of Xi'an Jiaotong University.Primary HTF were cultured by explant culture.Primary cells were identified by vimentin immunofluorescence staining and flow cytometry.The fibrosis model of HTF was established using 10 ng/ml transforming growth factor-β2 (TGF-β2). The cells were divided into normal control group cultured in culture medium, TGF-β2 group in culture medium containing TGF-β2, TGF-β2+ OMS group in culture medium containing TGF-β2 and OMS, and OMS group in culture medium containing OMS, and were cultured for 48 hours.Cell apoptosis was detected by flow cytometry with annexin V/PI staining.The early apoptosis, late apoptosis, and total apoptosis rates were analyzed.The protein expression of procaspase-9, cleaved caspase-9, bax and bcl-2 in the mitochondrial apoptosis pathway was detected by Western blot.The activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) was detected by colorimetry.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (No.2019-014).Results:Primary HTF were successfully isolated and cultured.The cultured cells were long spindle-shaped and positive for vimentin.The expression rate of vimentin in the primary cells was greater than 99%.A statistically statistical difference was found in the early apoptosis rate, late apoptosis rate, and total apoptosis rate among the four groups ( F=24.92, 3.96, 41.82; all at P<0.05). The early and total apoptosis rates were significantly higher in TGF-β2+ OMS group than normal control group and TGF-β2 group, and the late apoptosis rate in TGF-β2+ OMS group was significantly higher than that of normal control group (all at P<0.05). There were statistically significant differences in cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 among the four groups ( F=4.40, 7.98, 4.61; all at P<0.05). The bax/bcl-2 expression was significantly increased in TGF-β2+ OMS group in comparison with normal control group, and the expressions of cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 were significantly elevated in TGF-β2+ OMS group compared with TGF-β2 group (all at P<0.05). LDH activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (783.99±79.97), (913.16±196.86), (2 529.06±240.21), and (2 134.29±138.96) μmol/(min·L), respectively, showing a statistically significant difference ( F=24.95, P<0.05). Compared with normal control group and TGF-β2 group, LDH activity in TGF-β2+ OMS group was increased, and the differences were statistically significant (both at P<0.05). SOD activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (50.35±0.97), (41.61±4.56), (28.88±3.26), and (37.61±4.83) μmol/(min·L), respectively, showing a statistically significant difference ( F=5.71, P<0.05). SOD activity was reduced in TGF-β2+ OMS group compared with normal control group and TGF-β2 group, reduced in OMS group compared with normal control group, and the differences were statistically significant (all at P<0.05). Conclusions:AGTR1 blocker OMS can promote the apoptosis of HTF effectively.Mitochondrial apoptosis pathway mediated by bax/bcl-2/caspase-9 and oxidative stress pathway are the potential mechanisms that OMS regulates the apoptosis of HTF.

Advances in the treatment of infantile hemangiomas of the larynx / 临床耳鼻咽喉头颈外科杂志

Infantile hemangiomas are relatively common soft tissue tumors in infants and young children, with a prevalence of about 4.5% in full-term newborns. Subglottic Hemangioma （SGH） is a relatively rare type of hemangioma, and its special location often causes respiratory distress and potentially life-threatening conditions in infants. Therefore, it is necessary for clinicians to make an accurate diagnosis and formulate a detailed treatment plan based on the clinical manifestations, the auxiliary examinations, the medical history and the vital signs evaluation of patients.This review describes the pathophysiological mechanism of infantile hemangioma and provides a detailed discussion on commonly used treatment methods in detail.

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Propranolol: A migraine prophylactic since the 1960s / Propranolol: um profilático para enxaqueca desde 1960

Introduction: Propranolol was the first non-selective beta-adrenergic blocker to be developed. Initially it was used in the treatment of cardiovascular diseases, but since the 60's it has been used in the prevention of migraine. Objective: The objective of this study was to know the history of propranolol and its use as a migraine prophylactic. Methods: This study was an integrative literature review using articles with historical data on propranolol, from its origin in cardiology to its indication in the preventive treatment of migraine. Results: Propranolol was described in 1962 for the treatment of cardiovascular diseases. In the same decade, it was prescribed for the preventive treatment of migraine and, recently, included in the consensus of the Brazilian Headache Society. Conclusion: Although propranolol was initially synthesized for the treatment of heart disease, it has proved to be an effective drug in preventing migraine attacks

Introdução: O propranolol foi o primeiro bloqueador beta-adrenérgico não seletivo a ser desenvolvido. Inicialmente era utilizado no tratamento de doenças cardiovasculares, mas desde a década de 60 tem sido utilizado na prevenção de enxaquecas. Objetivo: O objetivo deste estudo foi conhecer a história do propranolol e seu uso como profilático para enxaqueca. Métodos: Este estudo foi uma revisão integrativa da literatura utilizando artigos com dados históricos sobre o propranolol, desde sua origem na cardiologia até sua indicação no tratamento preventivo da enxaqueca. Resultados: O propranolol foi descrito em 1962 para o tratamento de doenças cardiovasculares. Na mesma década, foi prescrito para o tratamento preventivo da enxaqueca e, recentemente, incluído no consenso da Sociedade Brasileira de Cefaleia. Conclusão: Embora o propranolol tenha sido inicialmente sintetizado para o tratamento de doenças cardíacas, provou ser um medicamento eficaz na prevenção de crises de enxaqueca

Short-Term Results of Ivabradine versus Metoprolol: The Effects on Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

A new strategy in lung/lobe isolation in patients with a lung abscess or a previous lung resection using double lumen tubes combined with bronchial blockers

The combined use of a double?lumen tube and a bronchial blocker can be very helpful in two different clinical scenarios: (1) in isolating not only the contralateral lung, but also the lobe/s of the same lung in which the infected lobe must be resected, (2) in preventing/treating hypoxemia because of the presence of a contralateral lobectomy. A cardiothoracic anesthesiologist must expertise this technique to avoid complications during surgery.

Bronchial Blocker and Double?Lumen Endotracheal Tube Combination to Facilitate Lung Isolation during Esophagectomy

Lung isolation is an essential anesthetic technique utilized in thoracic surgeries. We present a patient undergoing esophagectomy that developed an iatrogenic injury to the left mainstem bronchus that damaged the bronchial cuff of a left?sided double?lumen endotracheal tube (DLETT). A bronchial blocker (BB) was placed in the tracheal lumen of the DLETT as a rescue method to facilitate continued lung isolation. This unusual combination of a DLETT and a BB proved useful once the bronchial cuff was compromised and may serve as a viable solution to maintain lung isolation in similar circumstances

Nationwide surveillance for S-Metoprololtreatment effect on blood pressure control against sympathetic overdrive in Indian patients with hypertension (PROTECT)

Background:Patients with hypertension in India been reported with high heart rate owing to sympathetic overdrive (SO). Beta-blockers provides several positive effects to reduce SO in patients with hypertension. The aim of present survey studywasto understand current real-world prevalence of SO in Indian patients with hypertension and usage of beta-blocker therapy in them.Methods:A cross sectional, observational, questionnaire-based survey conducted across India between June 2020 to October 2020. A specially designed validated questionnaire was shared with 157 registered health care practitioners (HCP),their anonymous inputs were captured and analysed in qualitative manner. Categorical data was summarized by number (n) and percentage (%). Results:Total 157 HCP participated and completed the survey. Around 53% of HCP observed that patients with average heart rate above 75 beats/min were associated with negative prognosis. Around 43% of HCP reported that raised heart rate is associated with advancedage and increased body mass index (BMI). Two-third of HCP reported that tachycardia is associated with stage-2 hypertension and marked by restlessness and anxiety which is suggestive of SO. Over 70% HCP agreed that the HR below 75 beats/min is associated with good prognosis. Around 89% HCP reported beta-blockers as the drug of choice in patients with augmented SO. S-Metoprololwas reported to bethemost preferred beta-blocker agent and was recommended by 76% HCP in patients with hypertension and coexisting SO.Conclusions:SO been reported prevalent conditionin Indian patients with hypertension which likely worsensthe prognosis in these patients. Beta-blockers reported to be the preferred choice of anti-hypertensive and S-Metoprololseem to be themost preferred agent amongst the available beta-blockers against SO in patients with hypertension in India.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs

Background & objectives: In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. Methods: This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Results: Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Interpretation & conclusions: Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

Observational study of new-onset atrial fibrillation inpatients treated with Ivabradine alone versus Ivabradine and?-blocker drug (The BetaBrad Study)

Introduction: Ivabradine is a heart rate lowering agent by inhibiting Iƒ current in sinus node. It is approved for use in patients with angina and heart failure for heart rate control. Recently, the concern has grown over increased incidence of atrial fibrillation in patients treated with Ivabradine. Aims: We observed critically ill patients in the intensive care unit, treated with Ivabradine alone versus Ivabradine plus a ?-blocking agent, and compared the incidence of new-onset atrial fibrillation. Settings and Design: This was an observational, single-center study. Materials and Methods: We observed 40 patients who were divided into two groups. One group of patients was treated with Ivabradine (no other heart rate-controlling agent) and the other group was treated with Ivabradine plus a ?-blocker drug. We studied the incidence of atrial fibrillation in an observation period of 7 days in the intensive care unit along with other patient characteristics. We used appropriate analytical protocol to compare the two groups. Statistical Analysis Used: Student’s unpaired t test and Fisher’s exact probability test were applied. The value of P < 0.05 was considered statistically significant. Results: Although one patient treated with Ivabradine (and no other rate/rhythm controlling drug) had new-onset atrial fibrillation, there was no statistically significant increase in the incidence of atrial fibrillation in critically ill patients (during the observation period) treated with Ivabradine versus Ivabradine plus ?-blocker drug. Conclusion: Our preliminary research suggests the use of Ivabradine for heart rate control in critically ill patients is not associated with an increased incidence of new-onset atrial fibrillation. However, we recommend a further larger study on this subject.

Treatment of hypertension complicated with hyperuricemia / 中国临床药理学与治疗学

Hypertension and hyperuricemia often coexist, and have a high incidence and often incur great harm. The current guidelines recommend active control of uric acid and blood pressure levels. But patients with high uric acid and high blood pressure still need detailed guidelines to standardize the treatment to avoid incurring more drug-related side effects. This article reviews the epidemiology and clinical harm, the therapeutic target value, the consensus and controversy on therapeutic treatment of high blood pressure combined with high uric acid.

Application of β-blockers for hypertension / 中国临床药理学与治疗学

β-blockers are widely administered to patients with various cardiovascular diseases including hypertension. However, in recent years, studies have questioned or even denied the antihypertensive effect of β-blockers, which has caused confusion to cardiovascular clinicians. Based on the systematic analysis of a number of studies, the author believes that β-blockers still remain the status as the first-line antihypertensives.

Effects of 2-APB in skin wound healing in mice through down-regulation of TRPM7 / 中国临床药理学与治疗学

AIM: To explore the promoting effect of 2-APB on skin wound healing in mice and its potential mechanism. METHODS: KM mice were divided into 5 groups: control group, DMSO group, low (50 mg/L), medium (100 mg/L) and high (200 mg/L) concentration 2-APB group. On the back of each mouse's skin use a circular punch about 1 cm on both sides of the midline of the spine to make a skin wound with a diameter of 10 mm and as deep as the fascia. The control group was only wrapped with gauze and no drugs were applied; the DMSO group was applied 1 g DMSO/Vaseline ointment per day; in the 2-APB group, apply 1 g of 2-APB/Vaseline ointment at a corresponding concentration every day. Pictures were taken the next day to observe the healing, and the material was taken on the 21st day, HE staining was used to observe the pathological morphology of the wound and western blot to detect TRPM7, TGF-β, collagen-I and IL-1β expression. RESULTS: Compared with the control group and the DMSO group, different concentrations of 2-APB could significantly promote skin wound healing in mice (P<0.01), but there was no significant difference in wound healing rate between the DMSO group and the control group group. The results of HE staining showed that, compared with the control group group and the DMSO group, 2-APB could increase the collagen content of the wound and the thickness of the dermis (P<0.01), but there was no significant difference between the DMSO group and the control group group. At the same time, 2-APB could also significantly increase the expression of TGF-β and Col-I on the wound, and inhibit the expression of TRPM7 and IL-1β. CONCLUSION: Different concentrations of 2-APB (50, 100 and 200 mg/L) can promote skin wound healing, and its mechanism may be related to the inhibition of TRPM7.

Individualized precision therapy for patients with ischemic stroke and hypertension / 中国临床药理学与治疗学

AIM: To investigate the influence of CYP3A5 gene polymorphism on the anti-hypertensive efficacy of calcium channel blocker in patients with ischemic stroke and hypertension. METHODS: A total of 108 cases of ischemic stroke patients with hypertension were included and divided into experimental group and control group, and 54 cases in each group, the experimental group selected amlodipine tablets and levamlodipine tablets respectively according to the results of genetic testing, while the control group selected amlodipine tablets, which in order to investigate the antihypertensive efficacy of the two groups. RESULTS: The effective rate of experimental group and control group was 77.78% and 57.41% (P 0.05). In the experimental group, the antihypertensive effect of GG and AG genotype patients after taking amlodipine tablets was significantly higher than that of AA type patients, and GG type patients had a stronger antihypertensive effect than AG type patients after taking amlodipine tablets. CONCLUSION: CYP3A5 gene polymorphism is very important for blood pressure control by calcium channel blockers in patients with ischemic stroke and hypertension.