Pancreatic carcinoma (PC) is greatly induced by the KRAS gene mutation, but effective targeted delivery for gene therapy has not existed. Small interfering ribonucleic acid (siRNA) serves as an advanced therapeutic modality and holds great promise for cancer treatment. However, the development of a non-toxic and high-efficiency carrier system to accurately deliver siRNA into cells for siRNA-targeted gene silencing is still a prodigious challenge. Herein, polyethylenimine (PEI)-modified hydroxyapatite (HAp) nanoparticles (HAp-PEI) were fabricated. The siRNA of the KRAS gene (siKras) was loaded onto the surface of HAp-PEI via electrostatic interaction between siRNA and PEI to design the functionalized HAp-PEI nanoparticle (HAp-PEI/siKras). The HAp-PEI/siKras was internalized into the human PC cells PANC-1 to achieve the maximum transfection efficiency for active tumor targeting. HAp-PEI/siKras effectively knocked down the expression of the KRAS gene and downregulated the expression of the Kras protein in vitro. Furthermore, the treatment with HAp-PEI/siKras resulted in greater anti-PC cells’ (PANC-1, BXPC-3, and CFPAC-1) efficacy in vitro. Additionally, the HAp-PEI exhibited no obvious in vitro cytotoxicity in normal pancreatic HPDE6-C7 cells. These findings provided a promising alternative for the therapeutic route of siRNA-targeted gene engineering for anti-pancreatic cancer therapy.

Central nervous system (CNS) tuberculosis (TB) is a devastating and often life-threatening disease caused by Mycobacterium tuberculosis. Contezolid, a new oxazolidinone, has demonstrated potent antimycobacterial activity in both in-vivo and in-vitro studies, with lower toxicity than linezolid. However, pharmacokinetic data are still not available for contezolid in the CNS of patients with CNS TB. This article reports the steady-state concentrations of contezolid in serum and cerebrospinal fluid (CSF) of a patient receiving contezolid as part of multi-drug treatment for tuberculous meningoencephalitis. At weeks 7 and 11 (7 h post-dose) after initiation of contezolid therapy, the serum concentrations of contezolid were 9.64 mg/L and 9.36 mg/L, respectively. In CSF, the observed concentrations of contezolid were 0.54 mg/L and 1.15 mg/L, respectively. The CSF:serum concentration ratios were 0.056 and 0.123 at weeks 7 and 11, respectively. The observed concentrations in CSF were above the minimum inhibitory concentration of contezolid against M. tuberculosis, and were close to the estimated serum unbound fraction of contezolid (10%), suggesting that unbound contezolid has high CSF permeability.

AA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.

Objective: Studies have shown a correlation between gut microbiota and anxiety and depression levels. However, these studies are mainly animal studies or clinical studies of non-cancer patients, there is still a lack of relevant studies in cancer patients. The main objective of this trial was to analyze the correlation between probiotics and anxiety and depression levels in cancer patients.Methods: We screened all cancer patients consecutively admitted to the inpatient department of the First Affiliated Hospital, Zhejiang University School of Medicine in May 2020. A total of 292 cancer patients met our inclusion criteria. Then, we followed up all patients for 24 weeks. Patients who had incomplete data or loss of follow-up were excluded. In addition, in patients who took probiotics, those did not take probiotics consistently or did not take specific probiotics were excluded. Ultimately, the number of patients enrolled was 82 in probiotics cohort and 100 in non-probiotics cohort. The 17-item Hamilton Depression Scale (HAMD-17) questionnaire was used to measure the depression levels of the patients, and we also used Hamilton Anxiety Scale (HAMA) questionnaire to assess the patients’ anxiety levels. A logistic regression model was used to analyze whether the difference in baseline data of two cohorts would affect the final result.Results: Demographic and clinical characteristics of all cancer patients enrolled in probiotics cohort and non-probiotics cohort were similar except the cancer therapy (P = 0.004). According to the HAMA score, we divided cancer patients into non-anxiety group (HAMA score < 14) and anxiety group (HAMA score ≥ 14). Similarly, cancer patients were also divided into non-depression group (HAMD-17 score ≤ 7) and depression group (HAMD-17 score > 7). The results demonstrated that there was no statistical difference in the proportion of patients with anxiety (6.1 and 13.0%, respectively, P = 0.121) and depression (30.5 and 23.0%, respectively, P = 0.254) between probiotics and non-probiotics cohorts. The results of logistic regression model analysis further proved that the baseline difference in cancer therapy did not affect the conclusions.Conclusion: Our results still suggest that there is no significant correlation between probiotics and anxiety and depression levels in cancer patients. Therefore, we do not recommend supplementing probiotics for cancer patients to prevent anxiety and depression. Moreover, high-quality RCTs are also needed to further confirm the conclusions of this study.