The safety and effects of high- and low-volume polyethylene glycol bowel preparation methods before colonoscopy on bowel cleanliness: a systematic review and meta-analysis.

Background: Although both high- and low-volume polyethylene glycol (PEG) are widely used in intestinal preparation before colonoscopy, there is still controversy over the superiority of their cleaning effects. This meta-analysis sought to explore the safety and effects of high-volume PEG solution and low-volume PEG mixed solution on intestinal cleanliness before colonoscopy. Methods: The PubMed, EMBASE, and Cochrane Library databases were searched to retrieve relevant articles on the effects of high- and low-volume PEG mixture solutions on intestinal cleanliness from the inception of the databases to October 15, 2022. Two independent researchers screened the literature according to the predetermined inclusion and exclusion criteria, and extracted the required data separately. A bias risk assessment was conducted for each study using the relevant tools in the Cochrane Handbook. The included data were subjected to a meta-analysis using R 4.2.1 software. Results: This article includes a total of 15 studies involving a total of 5,847 patients. There was no difference in the cleanliness score, qualified rate of intestinal cleanliness and patient compliance between the high- and low-volume group. The patients in the low-volume PEG mixed solution group had a higher repeat willingness bowel cleansing rate than those in the high-volume PEG group [risk ratio (RR) =0.71, 95% confidence interval (CI): 0.62-0.82, P<0.01]. Compared with the low-volume group, the incidence of adverse reactions such as nausea, vomiting, and abdominal pain increased in the high-volume group (RR =1.38, 95% CI: 1.22-1.56, P<0.01; RR =1.79, 95% CI: 1.41-2.27, P<0.01; RR =1.05, 95% CI: 1.01-1.08, P<0.01). Conclusions: In the pre-colonoscopy preparation method for patients, although the high-volume PEG and low-volume PEG mixed regimen have similar effects on intestinal cleanliness, the low-volume mixed regimen has a higher willingness to repeat and a lower incidence of adverse reactions. In clinical practice, considering patient compliance and safety, a low-volume mixed regimen may be a more optimal option.

GOx-Powered Janus Platelet Nanomotors for Targeted Delivery of Thrombolytic Drugs in Treating Thrombotic Diseases.

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces. The PM-camouflaged design conferred excellent biocompatibility to the nanomotors and improved their targeting ability to thrombus. The Janus distribution of GOx also allows the uneven decomposition of glucose in biofluids to produce a chemophoretic motion, increasing the drug delivery efficiency of nanomotors. In addition, these nanomotors are located at the lesion site due to the mutual adhesion and aggregation of platelet membranes. Furthermore, thrombolysis effects of nanomotors are enhanced in static and dynamic thrombus as well as in mouse models. It is believed that the novel PM-coated enzyme-powered nanomotors represent a great value for thrombolysis treatment.

LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins.

Long noncoding RNAs (lncRNAs) have been widely proven to be involved in liver lipid homeostasis. Herein, we identify an upregulated lncRNA named lncRP11-675F6.3 in response to rapamycin treatment using a microarray in HepG2 cells. Knockdown of lncRP11-675F6. 3 leads to a significant reduction in apolipoprotein 100 (ApoB100), microsomal triglyceride transfer protein (MTTP), ApoE and ApoC3 with increased cellular triglyceride level and autophagy. Furthermore, we find that ApoB100 is obviously colocalized with GFP-LC3 in autophagosomes when lncRP11-675F6. 3 is knocked down, indicating that elevated triglyceride accumulation likely related to autophagy induces the degradation of ApoB100 and impairs very low-density lipoprotein (VLDL) assembly. We then identify and validate that hexokinase 1 (HK1) acts as the binding protein of lncRP11-675F6.3 and mediates triglyceride regulation and cell autophagy. More importantly, we find that lncRP11-675F6.3 and HK1 attenuate high fat diet induced nonalcoholic fatty liver disease (NAFLD) by regulating VLDL-related proteins and autophagy. In conclusion, this study reveals that lncRP11-675F6.3 is potentially involved in the downstream of mTOR signaling pathway and the regulatory network of hepatic triglyceride metabolism in cooperation with its interacting protein HK1, which may provide a new target for fatty liver disorder treatment.

Comparison of anxiety and depressive symptoms of head and neck cancer patients in a closed-loop management system before and during the 2019 coronavirus pandemic: a comparative study.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) poses an unprecedented challenge to health and the financial system, especially the healthcare of patients with cancer. However, the research on the negative effect of the pandemic on the anxiety and depressive symptoms of cancer patients in closed-loop is rarely reported at present. In view of the limitations of previous studies. In this study, we compared the anxiety and depressive symptoms of head and neck cancer patients in the closed-loop management system before and during the 2019 coronavirus pandemic. METHODS: In this comparative study, a total of 526 head and neck cancer patients (269 and 257 patients before and during the COVID-19 pandemic) were enrolled in the present study. The two groups of patients' median age (53 years, 52 years), female distribution (70.26%, 66.15%) and male distribution (29.74%, 33.85%) were analyzed before and after the COVID-19 epidemic. They received questionnaires using the standardized data forms of Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to collect the relevant data of patients for retrospective investigation. For data analysis, either the chi-squared test or Fisher's exact test was employed for categorical variables, and we described the time trend of psychological states before and after the outbreak with Cochran-Armitage trend (CAT) test. RESULTS: A total of 526 head and neck cancer patients were included in the final analysis; 26.85% and 50.19% of cases experienced anxiety and depression during the COVID-19 epidemic. In contrast, 18.22% and 33.46% of cases had experienced anxiety and depression before the pandemic. According to the statistical results, the prevalence of anxiety and depression in patients during the COVID-19 epidemic was higher compared to that of patients prior to the pandemic (P=0.018). More importantly, both anxiety and depression incidence trends increased significantly before and after the outbreak of COVID-19 (P=0.000). CONCLUSIONS: The present study demonstrates the significant impact of COVID-19 on the psychological states of cancer patients in the case of closed-loop management system, effectively indicating the need for appropriate changes in treatment decisions, enhanced psychotherapy, and interventions to reduce the incidence of anxiety, depression, and even suicide during this pandemic.

A Cohort Study on Associations between Fundus/intraocular Pressure Abnormality and Medical Check-up Items.

PURPOSE: To evaluate the associations between medical check-up items (MCI) for fundus and intraocular pressure abnormality (FIPA) diseases in the Department of Health Management Centre, the Fifth Affiliated Hospital of Sun Yat-sen University (DHMC-FHS). PATIENTS AND METHODS: Individuals who visited DHMC-FHS and underwent MCI between June 2017 to May 2019 were included, 3237 subjects. A total of 356 participants were diagnosed as FIPA and enrolled. The general clinical characteristics were collected. Diseases for FIPA diagnosed included five cohort, high intraocular pressure, diabetic retinopathy, hypertension fundus arteriosclerosis, large eye cup, and high myopia fundus changes. Possible impact factors of MCI included blood routine, B-ultrasound, heart rate, hypertension, hyperlipidemia, standard vision, cerebral arteriosclerosis, body mass, arterial/carotid arteriosclerosis, etc. Further, the Pearson's correlation coefficients and logistic regression analyses were used to examine associations between MCI and FIPA. RESULTS: The weighted study population who belonged to FIPA included 356 subjects. There were significant differences in age, IOP, habitual exercise, smoking, sleep duration (P˂0.05) between FIPA and without FIPA. And RBC, Hemoglobin, B-ultrasound abnormal event, heart rate, systolic pressure, diastolic pressure, TC, LDL-C, standard vision, cerebral arteriosclerosis, body mass index, carotid arteriosclerosis were positively correlated with high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes (P < .05). Possible prognosis risk factors, higher IOP, habitual exercise and more frequent smoking affect FIPA prognosis significantly [Odds ratio (OR) = 0.53, P = .01; OR = 0.13, P = .03; OR = 0.83; P = .04, respectively]. CONCLUSION: Of FIPA participants, high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes were shown a positive relationship with MCI. Control IOP, habitual exercise and less frequent smoking were regarded as positive associations with decreased FIPA. These findings could help us prevent and diagnose FIPA diseases in time via MCI.

Evaluation on the application of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency.

BACKGROUND: To evaluate the diagnostic value of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency (VBI) during clinical diagnosis and treatment METHODS: Eighty patients diagnosed with VBI in our hospital from June 2018 to December 2019 were randomly selected as the observation group, and 80 healthy people who received physical examination in the same period were selected as the control group. The abnormal rate, main performance and results, and the peak velocity of blood flow and vertebrobasilar artery blood flow of the two groups were compared. RESULTS: The abnormal rate of EEG and TCD in VBI patients was 38.75% (31/80) and the 93.75% (75/80), respectively. In TCD examination, ACA, PCA, MCA, and VA of both sides of the observation group were higher than those of the control group, while BA was lower than that of the control group (P < 0.05). The Vs, Vd, and Vm on both sides of BA and VA in the observation group were lower than those in the control group, while PI and RI were higher than those in the control group (P < 0.05). CONCLUSIONS: TCD examination is highly sensitive to the degree and pattern of cerebral ischemia in VBI patients. EEG examination will define the changes of brain cell function after cerebral ischemia. Therefore, EEG and TCD have their own advantages. The application of TCD and EEG can be considered in the early diagnosis, curative effect, and prognosis evaluation of VBI patients, so as to improve the accuracy of diagnosis and prognosis.

Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins.

Ocotillol-type sapogenins (OTS) are major ginsenoside metabolites in human hepatic tissue. In order to better utilize OTS and derivatives thereof as anti-inflammatory compounds, present study produced multiple novel 3-amino acid OTS derivatives and evaluated their anti-inflammatory activity in vitro. The nitric oxide (NO) inhibitory activity of these compounds was used for OTS structure-activity relationship (SAR) evaluations, revealing that both R/S stereochemistry at C-24 and the amino acid type at C-3 influence such NO inhibitory activity. This activity was highest for an N-Boc-protected neutral aliphatic amino acid derivative of 24R-OTS (5a), which performed better than even hydrocortisone sodium succinate in vitro. Compound 5a was also able to markedly suppress the LPS-induced upregulation of TNF-α, IL-6, iNOS, and COX-2 via the NF-κB and MAPK pathways. This suggests that OTS derivatives may be valuable anti-inflammatory compounds worthy of further preclinical evaluation.

Synthesis and Structure-Activity Relationship of Pyxinol Derivatives as Novel Anti-Inflammatory Agents.

Pyxinol, the main metabolite of 20S-protopanaxadiol in human liver, was chosen as a novel skeleton for the development of anti-inflammatory agents. Pyxinol derivatives modified at C-3, C-12, or C-25 and selected stereoisomers were designed, prepared, and investigated for in vitro anti-inflammatory activities. Structure-activity relationship (SAR), focused on skeleton, was analyzed based on their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis. The preliminary SAR results signified that the biological activity of the pyxinol derivatives is largely dependent on the R/S stereochemistry of pyxinol skeleton and the hydroxy at C-3 is a modifiable position. Among the tested compounds, the 3-oximinopyxinol (4a) exhibited the most potent NO-inhibitory activity and was even comparable to the steroid drug. Furthermore, compound 4a also significantly decreased LPS-induced TNF-α and IL-6 synthesis and iNOS and COX-2 expressions via the NF-κB pathway. This study proves that pyxinol is an interesting skeleton for anti-inflammatory drug discovery.

Design, synthesis, and discovery of ocotillol-type amide derivatives as orally available modulators of P-glycoprotein-mediated multidrug resistance.

Multidrug resistance (MDR) is a major cause of failure in cancer treatment, in which the overexpression of P-glycoprotein (Pgp) plays a crucial role. Herein, a novel class of ocotillol-type amide derivatives has been designed, synthesized, and evaluated for their ability to reverse MDR. The structure-activity relationship of the reversal activity was analyzed. Ten compounds showed promising chemo-reversal ability, among which the 24R-ocotillol-type amide derivative 6c with an N-Boc-hexanoyl unit exhibited the most potency in reversing paclitaxel resistance in KBV cells. Compound 6c could inhibit Pgp-mediated rhodamine123 efflux function via stimulating Pgp-ATPase activity and exhibited high binding affinity with Pgp in molecular docking studies. Importantly, compound 6c enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice after oral administration. These results indicate that ocotillol-type amide derivatives are promising lead compounds for overcoming MDR in cancer.