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The main characteristics of panic disorder (PD) include recurrent panic attacks and persistent worry, accompanied by other physical and cognitive symptoms. While recent studies have revealed that gut bacteria play an important role in anxiety and depression, little is known about the relationship between oral microbiota and PD. Therefore, the objective of this study was to explore a possible correlation between oral microbiota and PD. We conducted 16S rRNA sequencing to compare differences in the oral microbiota of patients with PD (n = 26) and healthy controls (n = 40). Patients with PD exhibited higher alpha diversity (abundance and evenness) in their oral microbiota than healthy controls, while analysis of beta diversity revealed that the two groups differed in microbial community composition. Moreover, the relative abundance of 61 genera differed between them. Overall, PD resulted in distinct oral microbial profiles that could be potential diagnostic markers and therapeutic targets.

Chemical-induced hematotoxicity is an important concern in the drug discovery, since it can often be fatal when it happens. It is quite useful for us to give special attention to chemicals which can cause hematotoxicity. In the present study, we focused on in silico prediction of chemical-induced hematotoxicity with machine learning (ML) and deep learning (DL) methods. We collected a large data set contained 632 hematotoxic chemicals and 1525 approved drugs without hematotoxicity. Computational models were built using several different machine learning and deep learning algorithms integrated on the Online Chemical Modeling Environment (OCHEM). Based on the three best individual models, a consensus model was developed. It yielded the prediction accuracy of 0.83 and balanced accuracy of 0.77 on external validation. The consensus model and the best individual model developed with random forest regression and classification algorithm (RFR) and QNPR descriptors were made available at https://ochem.eu/article/135149 , respectively. The relevance of 8 commonly used molecular properties and chemical-induced hematotoxicity was also investigated. Several molecular properties have an obvious differentiating effect on chemical-induced hematotoxicity. Besides, 12 structural alerts responsible for chemical hematotoxicity were identified using frequency analysis of substructures from Klekota–Roth fingerprint. These results should provide meaningful knowledge and useful tools for hematotoxicity evaluation in drug discovery and environmental risk assessment.

The resistance of Candida albicans (C. albicans) to classical antifungals has been increasing significantly and poses great challenges to clinical treatment. The objective of this research is to ev...

Purpose: The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients.Method: All renal transplant patients were divided into CYP3A5*3/*3 homozygotes (group I) and CYP3A5*1 allele carriers (CYP3A5*1/*1 + CYP3A5*1/*3) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C0) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C0/D.Results: In this study, a significant DDI between tacrolimus and nifedipine with respect to the CYP3A5*3 polymorphism was confirmed. In group I (n = 43), the C0/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); p = 0.002]. However, this difference was not detected in group II (n = 27) (p = 0.216). The co-administrated nifedipine and CYP3A5*3/*3 homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.Discussion: A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

Botulinum neurotoxins (BoNTs) block the release of a series of neurotransmitters, which are pivotal for neuron action. Intrahippocampal administration of BoNTs inhibits glutamate release, protects neurons against cell death, and attenuates epileptic seizures. Compared with intrahippocampal administration, intranasal delivery is less invasive and more practical for chronic drug administration. To assess whether intranasal administration is feasible, we examined the role of botulinum neurotoxin A (BoNT/A) in hippocampal neuronal injury after status epilepticus (SE) induced by pilocarpine. Our data showed BoNT/A could bypass the blood-brain barrier (BBB) and entered the olfactory bulb and hippocampal neurons. In addition, SE could result in up-regulation of pro-apoptotic proteins (Caspase-3, Bax), down-regulation of anti-apoptotic protein Bcl-2 and neuronal death in hippocampus. BoNT/A could suppress the expression of Caspase-3 and Bax, attenuate the decrease of Bcl-2, and inhibit hippocampal neuron death induced by SE. Meanwhile, there was no significant difference in cognitive behavior between the BoNT/A-pretreated rats and normal rats. Thus, we provided a more convenient and less invasive route for taking advantage of BoNT/A in the field of anti-epilepsy.

To analyze the characteristics and relative factors of headache and neck pain due to cervicocerebral artery dissection (CAD). A total of 146 consecutive patients with CAD in Zhengzhou, China (2010–2017) were observed and registered prospectively. There were 60 (60/146) cases who complained of headache and neck pain, and we analyzed the characteristics of pain according to their clinical features. For the 130 (130/146) patients with complete clinical laboratory data, they were divided into two groups according to pain, and the relative factors of pain were analyzed. The headache and neck pain in 60 CAD patients was mostly acute onset (98.3%), 70.6% (12/17) of patients with anterior circulation dissection and 88.4% (38/43) of patients with posterior circulation dissection complained of moderate to severe pain. 41.2% (7/17) of patients with anterior circulation dissection had temporal pain, while 46.5% (20/43) of the patients with posterior circulation dissection had occipital pain. There were 23.5% (4/17) and 32.6% (14/43) of patients with anterior and posterior circulation dissection complained of throbbing pain, respectively, 23.5% (4/17) and 20.9% (9/43) of patients with anterior and posterior circulation dissection complained of pulsating pain. The pain could occur in the ipsilateral (40.0%), bilateral (52.7%), or contralateral (7.3%) sites of the dissection. In the 130 patients, there were 56 cases (43.1%) in the pain group, and 74 cases (56.9%) in the non-pain group. Multivariate logistic regression analysis showed that female gender (OR 4.01, 95% CI 1.63–9.85, P = 0.002), posterior circulation (OR 3.18, 95% CI 1.39–7.28, P = 0.006), history of headache (OR 4.72, 95% CI 1.08–20.52, P = 0.039), and low-density lipoprotein less than 1.8 mmol/L (OR 2.90, 95% CI 1.15–7.34, P = 0.025) were risk factors of the occurrence of the pain related to CAD. The headache and neck pain caused by CAD is a moderate to severe pain occurring suddenly. The pain nature may be diverse but mostly like throbbing and pulsating. When the dissected artery is located in the posterior circulation, the pain is mostly in the occipital region, and mostly in the temporal region when the dissected artery is located in the anterior circulation. The pain can occur in ipsilateral, bilateral, or contralateral of the dissection. In addition, several factors might contribute to the occurrence of headache and neck pain.

Cervicocerebral artery dissection (CAD) is a major cause of ischemic stroke in young adults. There are many existing studies on determinants for CAD; however, they are still not totally defined. We conduct the study to further investigate the determinants for CAD based on ischemic stroke patients. 81 ischemic stroke patients with CAD were enrolled in the CAD stroke group and 84 ischemic stroke patients without CAD were enrolled in the non-CAD stroke group. Their clinical data, such as age, gender, vascular risk factors, headache and neck pain and clinical laboratory data, were collected to analyze the differences between the two groups. A total of 165 ischemic stroke patients were included. The mean age of CAD stroke group was (51.6 ± 12.4) years, and (55.5 ± 8.1) years in non-CAD stroke group, with a statistically significant difference (P = 0.017). The average level of triglycerides in CAD stroke group was (1.3 ± 0.7) mmol/L, and (1.7 ± 1.1) mmol/L in non-CAD stroke group, with a statistically significant difference (P = 0.012). There were 42.0% (34/81) of headache and neck pain in CAD stroke group and 22.6% (19/84) in non-CAD stroke group, with a statistically significant difference (P = 0.008). The key findings with significant difference were stratified and multivariate logistic regression analysis showed that age

R&D outsourcing is another management form which can relieve enterprises from complexly daily activities and strengthen enterprises' competitiveness with the exception of human resources outsourcing and financial outsourcing. However, there are great risks involved in R&D outsourcing. The paper aimed at determining key risks of R&D outsourcing and making countermeasures for avoiding them. The paper, based on the concept and connotation of R&D outsourcing, analyzed risks during outsourcing at a strategic level and concluded that risks of R&D outsourcing should focus on risk of business strategic analysis, risk of decision-making on R&D outsourcing, risk of selection and management of service provider and risk of performance evaluation on R&D outsourcing. Finally the paper proposed preventive measure against the risks.