Improved renal cancer prognosis among users of drugs targeting renin-angiotensin system

Purpose We explored renal cell cancer (RCC) survival among users of antihypertensive medication as hypertension is proposed to be a risk factor for RCC and ACE-inhibitors and angiotensin receptor blockers (ARBs) have been associated with improved prognosis of RCC. Methods Finnish cohort of 13,873 participants with RCC diagnosed between 1995–2012 was formed from three national databases. RCC cases were identified from Finnish Cancer Registry, medication usage from national prescription database and co-morbidities from Care Registry of Healthcare. Logistic regression was used to calculate odds ratios for metastatic tumor extent at the time of diagnosis. Risk of RCC specific death after diagnosis was analyzed using Cox regression adjusted for tumor clinical characteristics. Results A total of 5,179 participants died of RCC during the follow-up. No risk association was found for metastatic tumor extent for any drug group. ACE-inhibitors, but no other drug group were associated with decreased risk of RCC specific death overall (HR 0.88, 95% CI 0.82–0.95) compared to non-users. In time-dependent analysis high-dose use of ACE-inhibitors (392 Defined Daily Dose (DDD)/year), HR 0.54, 95% CI 0.45–0.66) and ARBs (786.1 DDD/year, HR 0.66, 95% CI 0.50–0.87) associated with improved RCC survival. No information of TNM-classification or tobacco smoking was available. Conclusion ACE-inhibitors and ARBs in high dose associated with improved RCC specific survival. This may reflect overall benefit of treating hypertension with medication targeting renin-angiotensin system (RAS) system among RCC patients. Further studies are needed to explore the role of RAS in RCC.

Dosage Modification of Traditional Chinese Medicine Prescriptions: An Analysis of Two Randomized Controlled Trials

Traditional Chinese medicine (TCM) prescriptions lack standardization due to the complex composition of the prescribed herbs, the unclear mechanism of the formulas, and a lack of scientific data to support the dose-response relationship. Here, we proposed a new clinical strategy of dosage modification for TCM prescriptions to evaluate the clinical efficacy and guide the clinical medication. This study used two TCM prescriptions for the treatment of newly diagnosed type 2 diabetes mellitus (T2DM) to explore the key indications and the most appropriate critical values of dosage modification by analyzing two randomized controlled trials (RCTs). In this study, the indications refer to a change in the indicators from baseline at a certain time point (week 4, week 8, week 12), which could predict the change in outcome indicators, and the critical values refer to the change ranges closely related to the decrease in HbA1c at week 12. In Study 1, the correlation analysis between the change range of indicators at three time points (weeks 4, 8, and 12) from baseline and the decrease in HbA1c at week 12 from baseline (HbA1c 012) was carried out to screen the related indications. Next, we evaluate the related indications and the respective critical values to determine the key indicators, indications, and the most appropriate critical value. We conducted a correlation between the change range of key indicators (obtained from the result of Study 1) at three time points from baseline and HbA1c 012 to screen the key indications in the drug group, high-dose group, and low-dose group in Study 2. Key indications with critical values were determined to investigate the most appropriate critical value in the three groups separately. In Study 1, the key indicator was FBG, the key indication was FBG 04, and the most appropriate critical value was 0.5 mmol/L. In Study 2, the key indication was FBG 04 and the most appropriate critical value was 0.6 mmol/L in the drug group. In the high-dose group, the key indication was FBG 04, and the most appropriate critical value was 0.3 mmol/L. In the low-dose group, the key indication was FBG08, and the most appropriate critical value was 0.1 mmol/L. In addition, we summarized a verification strategy for dosage modification.

A Study of Anxiety on Experimental Epileptic Rat Models using Dark Light Box

The word neurodegeneration refers to defects in neuronal structure and consequently its function. The main characteristics of these disorders are relentless progression and cognitive declination. Epilepsy is one of the neurodegenerative disorders, around 50 million people in the world are affected with. Though it is one of the major health problems in the present society, there are several gaps in understanding the consequences related to neurological disorders. As research works related to neurodegeneration is very much limited in India we have planned one as an initiative. We segregated 8 animal groups, each with 6 animals for this work. The animal groups are LC, CO, AC15, AC25, AC35, BA10, BA15 and BA20. This study was conducted on 10th day after the lesion by considering the day of lesion as day ‘1’ and the next day as day 2nd. All the animals were recovered completely within these 10 days and were put in the dark light box to analyse the anxiety level of the animals, so as to analyse the effect of the drug employed. This particular study clearly supported the efficacy of the drug as the drug group animals were less anxious or even behaved normal. Both the crude extract and the selected active principle have proved their efficacy by the study.

Effect and Mechanism of Lidocaine Pretreatment Combined with Dexmedetomidine on Oxidative Stress in Patients with Intracranial Aneurysm Clipping

This study aimed to explore the effect and mechanism of lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients with intracranial aneurysm clipping. Many studies have used various drugs such as lidocaine to explore the effect and mechanism of lidocaine pretreatment. A total of 80 patients with intracranial aneurysm clipping surgery were randomly divided into 4 groups: the single lidocaine group, single dexmedetomidine group, lidocaine combined with dexmedetomidine group, and control group. The thread embolism method was used to establish a stable intracranial aneurysm model of Hashimoto rats. Fifty adult rats were randomly divided into a sham operation group, ligation of the left common carotid artery and bilateral posterior branch of renal artery, lidocaine group, dexmedetomidine group, and lidocaine combined with dexmedetomidine group. The colorimetric method was used to determine the oxidative stress indicators in brain tissue: MDA content, SOD activity, and T-AOC content. The western blot method characterized the protein levels related to oxidative stress: nNOS, iNOS, and NADPH oxidase subunits p22phox, gp91phox, and p47phox. The differences in each index between the groups were statistically significant ( P < 0.05 ). Animal experiment results revealed that the content of MDA in the brain tissue of rats in the LD group was significantly lower than that in the single-drug group and sham group. The T-AOC and SOD concentrations in the LD group were significantly higher than those in the single-drug group and sham group, and the differences between the groups were statistically significant ( P < 0.05 ). The protein expression of the LD group was significantly lower than that of the drug-alone group and model group, and the difference between groups was statistically significant ( P < 0.05 ). To sum up, lidocaine pretreatment combined with dexmedetomidine can effectively maintain the hemodynamic stability of patients with intracranial aneurysm clipping and reduce postoperative oxidative stress response. Its mechanism of action may be related to the inhibition of oxidative stress damage mediated by nNOS, iNOS, and p22phox, gp91phox, and p47phox in the hippocampus. Our study has significant and applicable medical aspects in lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients.

Endobronchial Therapy With Gentamicin and Dexamethasone After Airway Clearance by Bronchoscopy in Exacerbation of Non-Cystic Fibrosis Bronchiectasis: A Real-World Observational Study

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB.Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017.Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p &lt; 0.001). Re-examination of chest HRCT within 4–6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group.Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

Evaluation of the effectiveness of dequalinium chloride vaginal tablets in aerobic vaginitis: A placebo-controlled study

Background: Aerobic vaginitis is a disturbance of vaginal homeostasis caused by the colonization of enteric bacteria. They are not clinically well-defined and do not have standard treatment regimes. Hence, the present study was conducted to evaluate the effectiveness of dequalinium chloride topical vaginal administration in aerobic vaginitis in a placebo-controlled manner. Materials and Methods: This study was conducted in a placebo-controlled manner to demonstrate the effectiveness of vaginal 10 mg dequalinium chloride. A total of 30 patients with different vaginal infections were included in the study. The patients included in the study were divided between the drug group and the placebo group and were treated with one vaginal tablet daily for 6 days. The total symptom score, which consists of the assessment of discharge, itching, and burning sensation, and the lactobacillus grade evaluated microscopically, was determined. Results: It was found that the effectiveness of dequalinium chloride was very high compared to placebo (92% vs. 0%). The reproduction frequency in the first visit was statistically significantly lower in the drug group compared to the placebo group (P < 0.001). Conclusion: It was found that dequalinium chloride is effective for the treatment of aerobic vaginitis. However, studies containing a larger sample group, including the long-term effects (efficacy and side effects) of the drug, should be conducted to prove our conclusion.

An Experimental Study to Evaluate the Anti-Diarrheal Activity of Bhuvaneshwara Rasa in Wistar Albino Rats

Atisara (Diarrhea) is most commonly encountered disease of the present era, due to unhealthy and irregular habits. Atisara (Diarrhea) finds a place as important disease in individual’s life as everyone suffers from it at least once in life time. Bhuvaneshwara rasa is a unique herbo-mineral formulation explained in Bhaishajya ratnavali indicated for all kinds of diarrhea cases. Bhuvaneshwara rasa is a potent formulation having Saindhava, Triphala, Yamani, Bilva peshika and Gruhadhooma. Materials and methods: Raw materials were screened and collected and the formulation selected for the present study Bhuvaneshwara rasa was prepared accordingly. Anti-diarrheal activity of Bhuvaneshwara rasa was evaluated experimentally in albino rats. Experimental study was conducted in 3 groups of animals for anti-diarrheal study each. Anti-diarrheal study was done by castor oil induced diarrhoea and castor oil induced enter-pooling method. Bhuvaneshwara rasa (test drug) and Loperamide are effective in controlling diarrheal episodes. Bhuvaneshwara rasa has shown significant Anti-diarrheal activity in both Castor oil -induced diarrhea and castor oil induced enteropooling, test drug effective than control. Result: Bhuvaneshwara rasa was prepared according to SOP. Test drug group have shown effect experimentally. Conclusion: Bhuvaneshwara rasa is a good anti-diarrheal drug. It can be administered in all types of Atisara.

Saikosaponin D Inhibits Peritoneal Fibrosis in Rats With Renal Failure by Regulation of TGFβ1/ BMP7 / Gremlin1/ Smad Pathway

Peritoneal dialysis (PD) can improve the quality of life of patients with kidney disease and prolong survival. However, peritoneal fibrosis can often occur and lead to PD withdrawal. Therefore, it is imperative to better understand how to inhibit and slow down progression of peritoneal fibrosis. This study aimed to investigate the regulatory effect of Saikosaponin d (SSD), a monomer extracted from the plant Bupleurum, on peritoneal fibrosis and the contribution of TGFβ1/BMP7/Gremlin1 pathway cross-talk in this process. To this aim, we used a model 5/6 nephrectomy and peritoneal fibrosis in rats. Rats were divided into four groups, namely a control group (saline administration); a model group (dialysate administration; group M); a SSD group (dialysate and SSD administration); and a positive drug group (dialysate and Benazepril Hydrochloride administration; group M + A). Histological analysis indicated that peritoneal fibrosis occurred in all groups. WB, ELISA, and PCR essays suggested that TGFβ1 and Gremlin1 levels in group M were significantly higher than those in group C, whereas BMP7 expression was significantly lower. TGFβ1, Gremlin1 and BMP7 levels were significantly lower in the group where SSD was administered than in the other groups. The expression of BMP7 in SSD group was significantly increased. In addition, levels of Smad1/5/8 as assessed by PCR, and levels of p-Smad1/5/8 expression as assessed by WB were also significantly higher in the SSD group than in the M group. Expression of vimentin and α-SMA, two important markers of fibrosis, was also significantly decreased. Our study suggests a role for the TGFβ1/BMP7/Gremlin1/Smad pathway in peritoneal fibrosis with potential therapeutic implications. Finally, our results also suggest that the monomer SSD may be able to reverse peritoneal fibrosis via regulation of the TGFβ1/BMP7/Gremlin1/Smad pathway.

Efficacy of mifepristone and GnRH-a in patients with endometriosis after operation

Objective: The effect of mifepristone and GnRH-a on patients with endometriosis after operation. Methods: 100 cases of endometriosis treated by laparoscopic surgery in our hospital from May 2017 to October 2019 were divided into GnRH-a group (34 cases), mifepristone group (33 cases) and non-drug group (33 cases) according to the numerical random method, and the treatment effect of the three groups was compared. Result: After the drug treatment, the cumulative recurrence rate of non misoprostone group and GnRH-a group was 18.18% and 21.21%, P > 0.05 between the two groups, and 33.33% between the two groups, P < 0.05. After treatment, FSH, LH and other hormone indexes in mifepristone group were compared with those before treatment (P > 0.05), while E2 levels were compared with those before treatment (P < 0.05); FSH, LH, E2 levels in GnRH-a group were compared with those before treatment (P < 0.05), and those in mifepristone group were compared with those after treatment (P < 0.05). After treatment, the complete remission rate of the patients in the non misoprostone group and the GnRH-a group were 51.52% and 55.88%, respectively, P > 0.05 for the comparison between the groups, and 36.36% for the comparison between the patients in the non misoprostone group and the GnRH-a group, P < 0.05 for the comparison between the two groups. There was no significant difference between the two groups (P > 0.05). Conclusion: Mifepristone and GnRH-a have good effect on patients with endometriosis after operation. They can effectively reduce the recurrence rate and adverse reactions after EMT.

Flavonoids from Scutellaria baicalensis Georgi Stems and Leaves Regulate the Brain Tau Hyperphosphorylation at M|ultiple Sites Induced by Composited Aβ in Rats

Background: Neurofibrillary tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's disease (AD) are the main pathomechanisms of neuronal degeneration, which can be used as a sign of brain disorder. It is positively correlated with the degree of cognitive impairment in AD. Objective: The objective of this study is to investigate the effect of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combined with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. Methods: The model of rats for AD was established by intracerebroventricular injection of Aβ25-35 and AlCl3 combined with RHTGF-β1. On day 45 after the operation, the Morris water maze was used to screen the rats’ memory impairment model for AD. The successful model rats were randomly divided into the model group and three-dose of drug group. The drug group rats were daily and orally SSF administrated for 38 days. Western blotting was used to detect the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in the hippocampus and cerebral cortex of rats. Results: Compared with the sham group, the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) was significantly increased in the hippocampus and cerebral cortex in the model group (P < 0.01). However, the three doses of 35, 70 and 140 mg/kg SSF regulated the expression of phosphorylated Tau protein at the above sites to varying degrees in the hippocampus and cerebral cortex (P < 0.01) induced by composited Aβ. Conclusion: SSF can significantly reduce the protein expression levels of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in rats’ brain induced by the intracerebroventricular injection of composited Aβ. These results demonstrated that the neuro-protection and the impaired memory improvement of SSF were due to the inhibition for the hyperphosphorylation of Tau protein at multiple sites.