Effects of oral targeted treatments in pulmonary arterial hypertension: A systematic review and meta-analysis.

Background: Although pulmonary arterial hypertension (PAH) is a fatal disease, specific drugs have been used to treat PAH. These drugs predominantly target these three pathobiological pathways: Endothelin receptor antagonist (ERA), nitric oxide (NO), and prostanoids pathways. In this review, we aimed to analyze the efficacy and safety of oral targeted treatments for PAH. Methods: The national library of medicine (MEDLINE), excerpta medica database (EMBASE), and Cochrane Central Register of Controlled Trials databases were searched. Randomized controlled trials that compared the oral targeted drugs with placebos were selected. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for variables with dichotomous outcomes, and standardized mean differences with continuous outcomes variables. Additionally, the mean of the differences for the 6-min walk distance (6MWD) was analyzed. Results: In total, 23 studies involving 7,121 patients were included in this study. These studies show that orally PAH-specific drugs could decrease the risk of clinical worsening events, with an OR of 0.55 (p < 0.001). Furthermore, these drugs could improve exercise capacity, showing a 21.74-m increase in 6MWD (95% CI: 17.53-25.95 m) and cause a greater amelioration of functional class (OR = 0.60, 95% CI: 0.47-0.76). Additionally, subgroup analysis indicated that compared with placebo, ERAs, and drugs in the NO pathway were most effective and safe, which are associated with an improvement in exercise capacity, 6MWD, and worsening events-free survival rate. Conclusion: Nitric oxide exhibited the most prominent clinical effect on exercise tolerance. However, in the subgroup analysis, oral targeted drugs of different pathways show applicability to different populations, which highlights the need for precise treatment in the clinical setting. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=297946], identifier [CRD 42022297946].

[Screening and follow-up for congenital heart disease in children aged 0-3 years in rural areas of Chongqing, China].

OBJECTIVE: To examine the incidence of congenital heart disease (CHD) in children aged 0-3 years in the rural areas of Chongqing, and to determine the suitable "screening-diagnosis-follow-up" system and screening indicators for CHD in these areas. METHODS: Children aged 0-3 years from rural areas of the Fuling Disctrict of Chongqing were selected by cluster sampling. Using the "screening-diagnosis-evaluation system" employed at the levels of village/town, district/county, and province/city, the children were screened for seven indicators, i.e., family history of CHD, dyspnea, cyanosis, unique facial features, other congenital malformations, heart murmurs, and blood oxygen saturation (SpO2<95%). Children who were positive for one or more indicators accepted echocardiography (ECG) for the diagnosis of CHD. CHD patients were evaluated for disease progression, given guided treatments, and followed-up by pediatric cardiologists. RESULTS: Screening was performed for 10 005 out of the 10 281 children enrolled in the study (97.32% response rate). Among the 175 children who were positive for the indicators, 166 underwent ECG and 60 (0.6‰) were diagnosed with CHD, including 46 cases of simple CHD (76.65%), 11 cases of combined CHD (18.33%), and 3 cases of complex CHD (5.00%). Of the 7 screening indicators, heart murmur had the largest area under the ROC curve for the diagnosis of CHD. In addition, a combination of screening indicators (heart murmur, unique facial features, and other congenital malformations) was most effective for screening out CHD. The CHD patients were given surgical or intervention treatments, and followed up for 6 to 18 months. Ten patients improved without treatment, 13 patients received interventional or surgical treatment, 1 patient died of non-cardiac reasons. The remaining 36 patients were subjected to further follow-up. CONCLUSIONS: Heart murmur alone and in combination with unique facial features and other congenital malformations are valuable tools for CHD screening in children aged 0-3 years. The "village/town-district/county-province/city" screening-diagnosis-evaluation systems are useful for the early detection, diagnosis, and treatment of CHD in infants and young children from the rural areas of Chongqing.

Increased efficiency of testicular tumor chemotherapy by ultrasound microbubble-mediated targeted transfection of siMDR1.

The MDR1 gene encoding P-glycoprotein (P-gp) is an ATP-dependent drug efflux transporter and is related to drug resistance of yolk sac tumors. Drug resistence may be an important factor for the low efficiency of chemotherapy in the treatment of testicular tumors. P-gp, encoded by the MDR1 gene, is an ATP-binding cassette transporter. P-gp exhibits high expression in capillary endothelial cells of the testis and prevents the intracellular accumulation of chemotherapy agents in testicular tumor cells, resulting in drug resistance. In the present study, we aimed to use specific siRNA to silence the expression of the MDR1 gene and P-gp, leading to the reversal of multidrug resistance of testicular tumors and contributing a suitable condition for chemotherapy. Ultrasound microbubble-mediated delivery is a safe and effective tool for gene delivery. In the present study, we demonstrated that ultrasound microbubble-mediated delivery effectively improved the siMDR1 gene transfection in interstitial capillary endothelial cells of the testis, inhibited the expression of P-gp and increased daunorubicin accumulation. The testis tumor model was successfully constructed by injecting 1x10(7) yolk sac tumor cells in 3-week-old Sprague-Dawley rats. Ultrasound microbubble-mediated siMDR1 gene therapy improved the effect of chemotherapy on the testicular tumors. The testicular volume was reduced, the number of tumor cells within the testicular tissues decreased, and pathological changes were mostly recovered. Therefore, the present study indicated that ultrasound microbubble-mediated siMDR1 gene therapy in vivo reversed drug resistance by regulating P-gp expression, providing a promising method for the treatment of testicular tumors.

[Comparison of cognitive functions and neuropsychiatric symptoms between patients with Parkinson's disease dementia and Alzheimer's disease].

OBJECTIVE: To compare the cognitive functions and neuropsychiatric symptoms of Parkinson's disease dementia (PDD) versus Alzheimer's disease (AD). METHODS: Patients fulfilling the diagnostic and statistical manual of mental disorders, 4(th) edition (DSM-IV) dementia diagnosis criteria were recruited into this case-control study. AD patients were diagnosed with the criteria of National Institute of Neurologic and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) while PDD was based upon the standards of Movement Disorder Society (MDS) Task Force. According to clinical dementia rating (CDR) score, they were divided into mild dementia (CDR score = 0.5/1) and moderate-to-severe dementia groups (CDR score = 2/3). World Health Organization-University of California, Los Angeles, auditory verbal learning test (WHO-UCLA AVLT), clock drawing test (CDT) and neuropsychiatric inventory (NPI) were performed. RESULTS: No significant difference in immediate memory, delayed memory or long-delayed recognition score was observed between PDD and AD patients (P > 0.05). CDT score was significantly lower in PDD patients (mild dementia group: 0.9 ± 0.9; moderate-to-severe dementia group: 0.6 ± 0.9) than that of AD patients (mild dementia group: 1.5 ± 0.7, P < 0.001; moderate-to-severe dementia group: 1.1 ± 0.6, P = 0.027) and this difference was more significant in mild dementia group. More than 70% of PDD patients reported at least one neuropsychiatric symptom. And also, in mild dementia group, compared with AD patients (frequency: 43.2% (16/37), NPI score = 5.7 ± 11.9), a higher frequency of neuropsychiatric symptoms and higher NPI scores were observed in PDD patients (frequency: 71.40% (25/35), NPI score = 8.4 ± 9.8). CONCLUSION: More severe impairment in visuospatial ability and executive function was present in PDD patients compared with AD patients. And neuropsychiatric symptoms were more common and severe in PDD patients.