Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor.

Aurora kinase (AURK) and heat shock factor 1 (HSF1) are commonly overexpressed in non-small cell lung cancer (NSCLC), correlating with poor prognosis. This study aims to assess the therapeutic potential of combining the Danusertib (Danu, AURK inhibitor) and KRIBB11 (HSF1 inhibitor) for NSCLC treatment. The effects of this combination were investigated in A549 cells and a tumor xenograft mouse model. The findings demonstrate that concurrent administration of Danu and KRIBB11 effectively impedes cell proliferation, induces apoptosis, and triggers G2/M cell cycle arrest. Moreover, the combination treatment upregulates pro-apoptotic proteins (Cleaved-caspase3, Cleaved-PARP, and Bax) while downregulating anti-apoptotic proteins (Bcl-2), as well as G2/M-related proteins (CDC2 and cyclin B1). Additionally, the combination treatment elevates reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential, and activates the DNA damage pathway. Interestingly, we discovered that the PI3K/AKT pathway is involved in mediating the effects of both Danu and KRIBB11. Furthermore, the combination treatment inhibits tumor growth and AKT signaling in the xenograft mouse model, increases levels of the tumor tissue oxidation product malondialdehyde (MDA), and induces DNA damage. To summarize, a potential therapeutic approach for NSCLC may involve dual inhibition of AURK and HSF1, resulting in the downregulation of the PI3K/AKT signaling pathway, and the activation of ROS-mediated mitochondrial and DNA damage pathways.

Early impairment of magnocellular visual pathways mediated by isolated-check visual evoked potentials in primary open-angle glaucoma: a cross-sectional study.

OBJECTIVE: To explore different performances in the magnocellular (MC) and parvocellular (PC) visual pathways in patients with primary open-angle glaucoma (POAG) and to objectively assess impairment in early stage of POAG. METHODS AND ANALYSIS: This is a cross-sectional study. MC and PC visual pathways were assessed using isolated-check visual evoked potential (ic-VEP). Visual acuity, intraocular pressure, fundus examination, optical coherence tomography and visual field were measured. Signal-to-noise ratios (SNRs), mediated by ic-VEP were recorded. The Spearman's correlation analysis was used to estimate the relationships between visual functions and structures. Receiver-operating-characteristic (ROC) curves were used to estimate the accuracy in detection of early POAG. RESULTS: 60 participants (30 early POAG eyes and 30 age-matched control subjects) were recruited. MC visual pathway showed a non-linear response function, while PC visual pathway was a linear response function as contrast increased. Early POAG eyes exhibited significantly weaker initial contrast gains and lower maximum responses in the MC visual pathway (p=0.001, p=0.004, respectively). The SNRs at 8% and 32% depths of modulation (DOM) were significantly correlated with temporal-side retinal nerve fibre layer (RNFL) thickness in early POAG in MC-biased stimulation (p=0.017, p=0.020, respectively). The areas under ROC of 16% DOM were 0.780 (sensitivity 80.0%, specificity 63.3%) with the cut-off SNR of 2.07. CONCLUSIONS: The MC visual pathway was damaged in the early stage of POAG. The SNRs at 8% and 32% DOM of MC-biased stimulation were significantly correlated with temporal-side RNFL thickness in early POAG, which helped in understanding the mechanisms of visual impairment in the early stage of POAG.

Duodenal-jejunal bypass surgery activates eNOS and enhances antioxidant system by activating AMPK pathway to improve heart oxidative stress in diabetic cardiomyopathy rats.

BACKGROUND: Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. METHODS: High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. RESULTS: DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. CONCLUSIONS: DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway-and not solely by improving blood glucose-to improve oxidative stress in the heart of diabetic cardiomyopathy rats.

Evaluation of a self-imaging OCT for remote diagnosis and monitoring of retinal diseases.

OBJECTIVES: To evaluate the feasibility and accuracy of a portable, self-imaging optical coherence tomography (OCT) for measuring central subfield thickness (CST) and achieving diagnostic concordance for retinal lesions compared with clinic-based spectral-domain OCT (SD-OCT). METHODS: This comparative, cross-sectional study was conducted between August 2020 and February 2021. Two groups of adult participants were recruited: (1) a selected cohort of 160 participants with confirmed diagnosis and (2) a consecutive cohort of 315 participants recruited randomly. All participants underwent self-imaging OCT examination, as well as standard OCT examination. CST was automatically calculated for comparisons between the two OCT devices. Diagnostic concordance for retinal lesions and the success rate of self-imaging were assessed within the consecutive cohort. RESULTS: In the selected cohort, self-imaging OCT images yielded consistent CST with SD-OCT, with a mean difference of 0.1±7.7 µm for normal eyes, 4.9±10.6 µm for macular oedema, -1.3±9.5 µm for choroidal neovascularisation, 5.0±7.8 µm for epiretinal membrane. The self-imaging OCT also demonstrated good repeatability, with a mean test-retest difference in CST of 0.7±3.9 µm and limits of agreement ranging from -6.9 to 8.3 µm. Additionally, within the consecutive cohort, interdevice κ values ranged for detecting various retinal lesions ranged from 0.8 to 1.0, except in the cases of retinal detachment (κ=0.5). All eyes (100%) in the selected cohort and 242 eyes (76.8%) in the consecutive cohort successfully completed self-imaging. Participants spent less time on self-imaging compared with SD-OCT operated by a technician (66.7±20.1 vs 73.3±32.5, p<0.01). A majority of participants (90%) found the self-imaging process 'easy' and 'comfortable'. CONCLUSIONS AND RELEVANCE: This study demonstrates that our self-imaging OCT and clinical-used SD-OCT are highly consistent not only in measuring the CST but also in identifying most retinal lesions.

Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

Cortical Reorganization After Optical Alignment in Strabismic Patients Outside of Critical Period.

Purpose: To measure visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortex organization, in older children and adults with horizontal concomitant strabismus before and after strabismus surgery. Methods: Using real-time eye tracking to ensure gaze-contingent display, we examined the peripheral visual crowding effects in older children and adults with horizontal concomitant strabismus but without amblyopia before and after strabismus surgery. Patients were asked to discriminate the orientation of the central tumbling E target letter with flankers arranged along the radial or tangential axis in the nasal or temporal hemifield at different eccentricities (5° or 10°). The critical spacing value, which is the minimum space between the target and the flankers required for correct discrimination, was obtained for comparisons before and after strabismus surgery. Results: Twelve individuals with exotropia (6 males, 21.75 ± 7.29 years, mean ± SD) and 15 individuals with esotropia (6 males, 24.13 ± 5.96 years) participated in this study. We found that strabismic individuals showed significantly larger critical spacing with nasotemporal asymmetry along the radial axis that related to the strabismus pattern, with exotropes exhibiting stronger temporal field crowding and esotropes exhibiting stronger nasal field crowding before surgical alignment. After surgery, the critical spacing was reduced and rebalanced between the nasal and temporal hemifields. Furthermore, the postoperative recovery of stereopsis was associated with the extent of nasotemporal balance of critical spacing. Conclusions: We find that optical realignment (i.e., strabismus surgery) can normalize the enlarged visual crowding effects, a reliable psychophysical index of cortical organization, in the peripheral visual field of older children and adults with strabismus and rebalance the nasotemporal asymmetry of crowding, promoting the recovery of postoperative stereopsis. Our results indicated a potential of experience-dependent cortical organization after axial alignment even for individuals who are out of the critical period of visual development, illuminating the capacity and limitations of optics on sensory plasticity and emphasizing the importance of ocular correction for clinical practice.

Complications of preventive loop ileostomy versus colostomy: a meta-analysis, trial sequential analysis, and systematic review.

BACKGROUND: Preventive colostomy is required for colorectal surgery, and the incidence of complications associated with ileostomy and colostomy remains controversial. This study aimed to compare the incidence of postoperative complications between ileostomy and colostomy procedures. METHODS: Data analysis was conducted on 30 studies, and meta-analysis and trial sequential analysis (TSA) were performed on five studies. The basic indicators, such as stoma prolapse, leak, wound infection, ileus, and a series of other indicators, were compared. RESULTS: No statistically significant differences were observed with complications other than stoma prolapse. Meta-analysis and TSA showed that the incidence of ileostomy prolapse was lower than that of colostomy prolapse, and the difference was statistically significant. Apart from the four complications listed above, the general data analysis showed differences in incidence between the two groups. The incidence of skin irritation, parastomal hernia, dehydration, pneumonia, and urinary tract infections was higher with ileostomy than with colostomy. In contrast, the incidence of parastomal fistula, stenosis, hemorrhage, and enterocutaneous fistula was higher with colostomy than with ileostomy. CONCLUSIONS: There were differences in the incidence of ileostomy and colostomy complications in the selected studies, with a low incidence of ileostomy prolapse. PROSPERO REGISTRATION NUMBER: CRD42022303133.

Monocular information for perceiving large egocentric distance: A comparison between monocularly blind patients and normally sighted observers.

The debate surrounding the advantages of binocular versus monocular vision has persisted for decades. This study aimed to investigate whether individuals with monocular vision loss could accurately and precisely perceive large egocentric distances in real-world environments, under natural viewing conditions, comparable to those with normal vision. A total of 49 participants took part in the study, divided into three groups based on their viewing conditions. Two experiments were conducted to assess the accuracy and precision of estimating egocentric distances to visual targets and the coordination of actions during blind walking. In Experiment 1, participants were positioned in both a hallway and a large open field, tasked with judging the midpoint of self-to-target distances spanning from 5 to 30 m. Experiment 2 involved a blind walking task, where participants attempted to walk towards the same targets without visual or environmental feedback at an unusually rapid pace. The findings revealed that perceptual accuracy and precision were primarily influenced by the environmental context, motion condition, and target distance, rather than the visual conditions. Surprisingly, individuals with monocular vision loss demonstrated comparable accuracy and precision in perceiving egocentric distances to that of individuals with normal vision.

Mussel- and nacre-inspired dual-bionic alginate-based hydrogel coating with multi-matrix applicability, high separation stability and antifouling performance for oil/water separation.

Natural hydrogel-modified porous matrices with superwetting interfaces are ideal for oil/water separation. In this study, inspired by two marine organisms, a novel hydrogel coating with multi-matrix suitability, high oil/water separation capability and antifouling properties was developed. Specifically, inspired by mussel byssus, hydrogel coating was successfully deposited on porous matrix surface based on the introduction of tannic acid (TA). Moreover, inspired by the "brick and mortar" microstructure of Pinctada nacre, silica particles were in-situ synthesized in the sodium alginate (SA)/Ca2+ hydrogel to provide the filling effect and to increase strength. Furthermore, Sodium alginate-tannic acid-tetraethyl orthosilicate (SA-TA-TEOS) hydrogel coating-modified membrane exhibited super-hydrophilic and underwater super-oleophobic performance (underwater oil contact angle >150°), and achieved efficient oil/water separation for four oil/water emulsions (flux = 493-584 L·m-2·h-1 and rejection = 97.3-99.5 %). The modified membrane also demonstrated good anti-fouling performance and flux recovery. Notably, hydrogel coating-modified non-woven fabric also had high oil/water separation capacity (rejection >98 %) and cyclic stability, which proved the universal applicability of this hydrogel coating. In short, this work provides new insights into the fabrication of hydrogel coating-modified porous materials based upon a marine organism biomimetic strategy, which has potential applications in separating oil/water emulsions in industrial scenarios.

Targeted reaching with monocular depth information and haptic feedback: Comparing between monocular patients and normally sighted observers.

Monocular blindness impairs visual depth perception, yet patients seldom report difficulties in targeted actions like reaching, walking, or driving. We hypothesized that by utilizing monocular depth information and calibrating actions with haptic feedback, monocular patients can perceive egocentric distance and perform targeted actions. We compared targeted reaching in monocular patients, monocular-viewing, and binocular-viewing normal controls. Sixty observers reached either a far or a near target, calibrating reaches to the near target with accurate or false feedback while leaving reaches to the far target uncalibrated. Reaching accuracy and precision were analyzed. Results indicated no difference in reaching accuracy between monocular patients and normal controls; all groups initially underestimated distances before until calibration. Monocular patients responded to calibration sensitively, achieving accuracy in calibrated reaches and generalizing this effect to uncalibrated distances. Thus, with monocular depth information and haptic feedback, monocular patients could perceive distance and accomplish targeted reaching.

Swab Pressing vs Stromal Hydration to Prevent Incision Leakage and Transient Collapse of Anterior Chamber in Phacoemulsification: A Randomized Clinical Trial.

Importance: During phacoemulsification, incision leakage and the subsequent anterior chamber collapse often occur after the withdrawal of the handpiece, which cannot be prevented by current sealing techniques. A new technique called swab pressing is proposed here to apply pressure with a cotton swab to seal the incision immediately, but efficacy remains unknown. Objective: To determine if swab pressing is noninferior to stromal hydration, the current practice, in sealing incisions in phacoemulsification for age-related cataract. Design, Setting, and Participants: This noninferiority randomized controlled clinical trial was conducted between February 2022 and September 2022 at the Zhongshan Ophthalmic Center, Guangzhou, China. Patients aged 60 to 90 years with age-related cataract were enrolled. Interventions: Participants were randomly assigned (1:1) to receive swab pressing or stromal hydration. All surgeries were performed by a single experienced surgeon who was unmasked to the assignment. Main Outcomes and Measures: The proportion of closed clear corneal incisions evaluated using intraoperative optical coherence tomography. Results: A total of 126 eyes of 126 participants were randomized into the swab pressing group (63 [50%]) and stromal hydration group (63 [50%]). The mean (SD) age of participants was 69.2 (6.14) years and 70.1 (7.67) years in the pressing and stromal hydration groups, respectively. A total of 39 participants (61.9%) in the pressing group and 35 (55.6%) in the modified group were female. The proportion of closed incisions was 96.8% (61 of 63) in the swab pressing group and 93.7% (59 of 63) in the stromal hydration group. Noninferiority was met, as the lower 95% CI of -5.83 percentage points was greater than the prescribed noninferiority margin of -6.60 percentage points (difference, 3.17 percentage points; 95% CI, -5.83 to 12.18 percentage points). The rate of anterior chamber collapse (pressing: 0 of 63 vs stromal hydration: 35 of 63 [55.6%]; P < .001) was lower in the swab pressing group. There were no differences between the 2 groups in the proportion of closed incisions and central anterior chamber depth at postoperative hour 1 and day 1. Conclusions and Relevance: In this study, swab pressing was noninferior to stromal hydration in sealing clear corneal incisions in phacoemulsification for age-related cataract. While this trial involved only 1 surgeon who was not masked to the interventions, the results suggest that swab pressing is feasible and further investigations would be warranted to determine if it prevents the intraoperative transient collapse of anterior chamber or affects visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05242653.

Visual Crowding Reveals Field- and Axis-Specific Cortical Miswiring After Long-Term Axial Misalignment in Strabismic Patients Without Amblyopia.

Purpose: Inspired by physiological and neuroimaging findings that revealed squint-induced modification of cortical volume and visual receptive field in early visual areas, we hypothesized that strabismic eyes without amblyopia manifest an increase in critical spacing of visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortical organization. Methods: We used real-time eye tracking to ensure gaze-contingent display and examined visual crowding in patients with horizontal concomitant strabismus (both esotropia and exotropia) but without amblyopia and age-matched normal controls. Results: Nineteen patients with exotropia (12 men, mean ± SD = 22.89 ± 7.82 years), 21 patients with esotropia (10 men, mean ± SD = 23.48 ± 6.95 years), and 14 age-matched normal controls (7 men, mean ± SD = 23.07 ± 1.07 years) participated in this study. We found that patients with strabismus without amblyopia showed significantly larger critical spacing with nasotemporal asymmetry in only the radial axis that related to the strabismus pattern, with exotropia exhibiting stronger temporal hemifield crowding and esotropia exhibiting stronger nasal hemifield crowding, in both the deviated and fixating eyes. Moreover, the magnitude of crowding change was related to the duration and degree of strabismic deviation. Conclusions: Using visual crowding as a psychophysical index of cortical organization, our study demonstrated significantly greater peripheral visual crowding with nasotemporal asymmetry in only the radial axis in patients with strabismus without amblyopia, indicating the existence of hemifield- and axis-specific miswiring of cortical processing in object recognition induced by long-term adaptation to ocular misalignment.

Use of a tissue clearing technique combined with retrograde trans-synaptic viral tracing to evaluate changes in mouse retinorecipient brain regions following optic nerve crush.

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

Effect of transanal drainage tube on prevention of anastomotic leakage after anterior rectal cancer surgery taking indwelling time into consideration: a systematic review and meta-analysis.

Background: Placement of an indwelling transanal drainage tube (TDT) to prevent anastomotic leakage (AL) after anterior rectal cancer surgery has become a routine choice for surgeons in the recent years. However, the specific indwelling time of the TDT has not been explored. We performed this meta-analysis and considered the indwelling time a critical factor in re-analyzing the effectiveness of TDT placement in prevention of AL after anterior rectal cancer surgery. Methods: Randomized controlled trials (RCTs) and cohort studies which evaluated the effectiveness of TDT in prevention of AL after rectal cancer surgery and considered the indwelling time of TDT were identified using a predesigned search strategy in databases up to November 2022. This meta-analysis was performed to estimate the pooled AL rates (Overall and different AL grades) and reoperation rates at different TDT indwelling times and stoma statuses. Results: Three RCTs and 15 cohort studies including 2381 cases with TDT and 2494 cases without TDT were considered eligible for inclusion. Our meta-analysis showed that the indwelling time of TDT for ≥5-days was associated with a significant reduction (TDT vs. Non-TDT) in overall AL (OR=0.46,95% CI 0.34-0.60, p<0.01), grade A+B AL (OR=0.64, 95% CI 0.42-0.97, p=0.03), grade C AL (OR=0.35, 95% CI 0.24-0.53, p<0.01), overall reoperation rate (OR=0.36, 95%CI 0.24-0.53, p<0.01) and that in patients without a prophylactic diverting stoma (DS) (OR=0.24, 95%CI 0.14-0.41, p<0.01). There were no statistically significant differences in any of the abovementioned indicators (p>0.05) when the indwelling time of TDT was less than 5 days. Conclusion: Extending the postoperative indwelling time of TDT to 5 days may reduce the overall AL and the need for reoperation in patients without a prophylactic DS. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407451, identifier CRD42023407451.

Engineering a superwetting membrane with spider-web structured carboxymethyl cellulose gel layer for efficient oil-water separation based on biomimetic concept.

Superhydrophilic and underwater superoleophobic membranes have recently attracted significant interest as materials for effective oil-water emulsion separation. In this work, a superwetting membrane with a spider web structured gel layer was designed for efficient oil-water separation. Biomaterial, carboxymethyl cellulose (CMC), was used as the raw material, a spider web structured gel layer was constructed on the PVDF membrane surface by heat-treatment and chemical cross-linking. The hydrophilic gel layer imparted excellent superhydrophilic and underwater superoleophobic properties to the membrane, while the special spider web structure improved the membrane mechanical stability. The fabricated membrane exhibited superhydrophilicity and underwater superoleophobicity. Among different CMC concentration-modified membranes, the M-0.5 membrane containing 0.5 wt% CMC exhibited a flux of 612 L·m-2 h-1 during dichloromethane oil-water emulsion separation, which was 4.2-fold higher than that of the pristine PVDF membrane, while the membrane showed efficient oil-water separation capacity. Additionally, the water flux recovery reached as high as 93.3 %, and oil rejection attained 99.1 %. Meanwhile, the spiderweb-structured gel layer on the membrane surface displayed good mechanical stability. In summary, this novel membrane-modification method, inspired by the spider web structure, was simple, cost effective and environmentally friendly, thereby making it promising for future preparation of highly efficient oil-water emulsion separation membranes.

Comparative pharmacokinetics and urinary excretion of arsenic and mercury after oral administration of realgar, cinnabar and AnGongNiuHuang Pill to rats.

Realgar- and cinnabar-containing AnGongNiuHuang Pill (AGNHP) is widely used for treating encephalopathy syndrome. However, it raises great safety concerns due to the adverse effects reported by arsenic or mercury poisoning. Although AGNHP has been generally recognized, little is known about the metabolism of arsenic and mercury and their resulting potential health risk in vivo. Thus, comparative pharmacokinetics and urinary excretion of arsenic and mercury were conducted in rats after oral administration of realgar, cinnabar and AGNHP, respectively. The contents of arsenic and mercury in rat blood and urine were determined by hydride-generation atomic fluorescence spectrometry (HG-AFS) after wet digestion. AGNHP significantly reduced the absorption of arsenic in blood and promoted urinary arsenic excretion. Whereas, it increased the blood mercury absorption and reduced urinary mercury excretion. No significant toxicity was observed in the clinical dose range of AGNHP. However, excessive exposure to arsenic and mercury may still pose risks especially by long-term or excessive medication. The results are helpful for the rational clinical applications of realgar- and cinnabar-containing TCMs.

GPR37 promotes cancer growth by binding to CDK6 and represents a new theranostic target in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is associated with poor prognosis. Identifying novel cancer targets and helpful therapeutic strategies remains a serious clinical challenge. This study detected differentially expressed genes in The Cancer Genome Atlas (TCGA) LUAD data collection. We also identified a predictive DNA biomarker, G protein-coupled receptor 37 (GPR37), which was verified as a prognostic biomarker with a critical role in tumor progression. In human LUAD specimens and microarray analyses, we determined that GPR37 was significantly upregulated and associated with a poor prognosis. GPR37 downregulation markedly inhibited the proliferation and migration of LUAD both in vitro and in vivo. Mechanistically, GPR37 could bind to CDK6, thereby facilitating tumor progression in LUAD by inducing cell cycle arrest at the G1 phase. GPR37 also facilitates tumorigenesis in xenograft tumors in vivo. High-throughput screening for GPR37-targeted drugs was performed using the Natural Products Library, which revealed the potential of Hypocrellin B to inhibit GPR37 and cell growth in LUAD. We demonstrated that Hypocrellin B suppressed LUAD cell proliferation and migration both in vitro and in vivo via GPR37 inhibition. Collectively, our findings reveal the role of GPR37 in LUAD progression and migration and the potential of GPR37 as a target for the treatment of LUAD. Thus, the specific inhibition of GPR37 by the natural product Hypocrellin B may possess the potential for the treatment of LUAD.

Bile Acid Detection Techniques and Bile Acid-Related Diseases.

Bile acid is a derivative of cholinergic acid (steroidal parent nucleus) that plays an important role in digestion, absorption, and metabolism. In recent years, bile acids have been identified as signaling molecules that regulate self-metabolism, lipid metabolism, energy balance, and glucose metabolism. The detection of fine changes in bile acids caused by metabolism, disease, or individual differences has become a research hotspot. At present, there are many related techniques, such as enzyme analysis, immunoassays, and chromatography, that are used for bile acid detection. These methods have been applied in clinical practice and laboratory research to varying degrees. However, mainstream detection technology is constantly updated and replaced with the passage of time, proffering new detection technologies. Previously, gas chromatography (GS) and gas chromatography-mass spectrometry (GC-MS) were the most commonly used for bile acid detection. In recent years, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has developed rapidly and has gradually become the mainstream bile acid sample separation and detection technology. In this review, the basic principles, development and progress of technology, applicability, advantages, and disadvantages of various detection techniques are discussed and the changes in bile acids caused by related diseases are summarized.

Medication Adherence and Common Barriers for Caregivers of Preschool Children with Pediatric Glaucoma.

Purpose: To investigate the medication adherence among caregivers of preschool children with pediatric glaucoma and to elucidate common barriers leading to poor adherence. Methods: A cross-sectional study. Caregivers of preschool children with pediatric glaucoma completed a questionnaire on demographic information of caregivers, demographic and disease characteristics of children, caregivers-reported medication adherence (by an adapted Morisky Adherence Scale), and possible 13 barriers. Results: Overall 132 questionnaires were considered valid. Thirty-six percent of all reported poor medication adherence. Caregivers' age and self-evaluated knowledge about pediatric glaucoma showed a significant difference between the adherent and nonadherent groups (P < 0.05). Nineteen percent of all reported only one barrier as important, 65% cited multiple barriers, and 16% cited no barriers. Anxiety and depression were cited as important by most caregivers in both groups. Univariate logistic regression analysis demonstrated that difficulty with the acquisition of medications (OR, 2.5; 95% CI, 1.1-5.7; P=0.025), difficulty with medication schedule (OR, 2.3; 95% CI, 1.0-5.0; P=0.043), and high expenses for medications (OR, 4.8; 95% CI, 1.4-15.9; P=0.011) were significantly associated with higher odds of poor adherence. Conclusions: Over one-third of caregivers of preschool children with pediatric glaucoma were in poor medication adherence. Nearly two-thirds of caregivers cited multiple barriers simultaneously as important hindrances to medication usage. Anxiety and depression, difficulty with the acquisition of medications, difficulty with the medication schedule, and high expenses for medications were prominent barriers. Individualized solutions should be provided according to reported barriers by each caregiver and the other most common barriers.