Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract.

Bilestones are solid masses found in the gallbladder or biliary tract, which block the normal bile flow and eventually result in severe life-threatening complications. Studies have shown that bilestone formation may be related to bile flow dynamics and the concentration level of bile components. The bile flow dynamics in the biliary tract play a critical role in disclosing the mechanism of bile stasis and transportation. The concentration of bile composition is closely associated with processes such as nucleation and crystallization. Recently, microfluidic-based biosensors have been favored for multiple advantages over traditional benchtop detection assays for their less sample consumption, portability, low cost, and high sensitivity for real-time detection. Here, we reviewed the developments in bile dynamics study and microfluidics-based bile component detection methods. These studies may provide valuable insights into the bilestone formation mechanisms and better treatment, alongside our opinions on the future development of in vitro lithotriptic drug screening of bilestones and bile characterization tests.

Analysis and numerical investigation of bile flow dynamics within the strictured biliary duct.

The mechanics of bile flow in the biliary system plays an important role in studying bile stasis and gallstone formation. Bile duct stricture is an abnormal phenomenon that refers to the bile duct getting smaller or narrower. The main objective of this study is to study the influence of stricture on bile flow dynamics using numerical methods. We employed a numerical Computational Fluid Dynamics model of the bile flow within a strictured hepatic duct. We studied and compared the influence of stricture severity, stricture length, eccentricity, and bile flow property on the bile flow dynamics. The bile flow velocity, pressure distribution, pressure drop, and wall shear stress are provided in detail. The stricture alters the normal bile flow pattern and increases flow resistance. At the location upstream and downstream of the stricture, bile flow slows down. In the area of the stricture throat, bile flow is accelerated, and recirculation forms behind the stricture. The maximum pressure drop of the biliary system increases with the stricture length. The eccentricity makes the flow deflect away from the duct's centerline. The behavior of the deflected flow is significantly altered downstream of the stricture. Such bile flow behavior as deceleration and recirculation may lead to cholestasis. Stricture alters bile flow in the biliary tract, causing changes in biliary hydrodynamic indexes, which could potentially serve as an omen for gallstone formation and other related diseases. The consideration of the bile duct stricture could lead to better patient stratification.

pH Regulator on Digital Microfluidics with Pico-Dosing Technique.

Real-time pH control on-chip is a crucial factor for cell-based experiments in microfluidics, yet difficult to realize. In this paper, we present a flexible pH regulator on a digital microfluidic (DMF) platform. The pico-dosing technology, which can generate and transfer satellite droplets, is presented to deliver alkali/acid into the sample solution to change the pH value of the sample. An image analysis method based on ImageJ is developed to calculate the delivered volume and an on-chip colorimetric method is proposed to determine the pH value of the sample solution containing the acid-base indicator. The calculated pH values show consistency with the measured ones. Our approach makes the real-time pH control of the on-chip biological experiment more easy to control and flexible.

Knowledge of glaucoma and associated factors among primary glaucoma patients in Kunming, China.

BACKGROUND: To investigate the level of knowledge, attitude, and practices about glaucoma and associated factors among primary glaucoma patients in Kunming, China. METHODS: A hospital-based study was conducted on 93 patients from the First Affiliated Hospital of Kunming Medical University. Interviewer-administered questionnaires were used to collect data after written informed consent. Data were analyzed by SPSS 19.0. Univariate and multivariate logistic regression models were used to identify factors. A Chi-square test was used to analyze the association between knowledge of glaucoma and medication compliance, Mann-Whitney U test was performed to assess the relationship between knowledge of glaucoma and quality of life in patients with glaucoma. P-value < 0.05 was considered statistically significant. RESULTS: Among 93 patients, 55 (59.14%) were aware of glaucoma, 48 (51.61%) had good knowledge of glaucoma, while 45 (48.39%) had poor knowledge. Younger age and duration of glaucoma were associated positively with knowledge of glaucoma. 87 (93.54%) patients got knowledge of their disease from doctors. 79.17% of respondents could use all the anti-glaucoma medications on time, out of which 54.17% had good knowledge of glaucoma while 25.00% had poor knowledge of glaucoma. 30.56% of respondents used to stop anti-glaucoma medications on their own out of which only 9.72% had good knowledge of glaucoma while 20.83% had poor knowledge of glaucoma. Patients with good knowledge of glaucoma had lower scores on the Glaucoma Quality of Life-15 questionnaire. Thus, the compliance to anti-glaucoma medications and glaucoma-related quality of life were better in patients with good knowledge. CONCLUSIONS: The level of knowledge of glaucoma among patients in Kunming is relatively low. Improving knowledge with suitable content for patients through effective multiple means such as the mass media rather than relying only on ophthalmologists may be a veritable first step in combating blindness from glaucoma and enhancing patients' quality of life.

Near-infrared laser-controlled nitric oxide-releasing gold nanostar/hollow polydopamine Janus nanoparticles for synergistic elimination of methicillin-resistant Staphylococcus aureus and wound healing.

Recently, nitric oxide (NO) has received increasing interest in combat against bacteria-induced infections because of its ability to sensitize and enhance the antibacterial effectiveness of many therapeutic approaches such as antibiotics. However, high-efficient loading and controlled release of NO remain a big challenge. In the present work, a type of gold nanostar/hollow polydopamine Janus nanostructure (GNS/HPDA JNPs) with precise near infrared (NIR)-controlled NO release property was fabricated using a facile seed-mediated method. Upon NIR laser irradiation, the NO-releasing GNS/HPDA JNPs (GNS/HPDA-BNN6) exhibited a synergistic photothermal and NO antibacterial effect by significantly inhibiting the growth and biofilm formation of both Gram-negative and Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA). An in-depth mechanism study revealed that two pathways were mainly involved in the synergistic photothermal and NO antibacterial effect. In one pathway, the synergistic effect severely destroyed the bacterial membrane by causing leakage of intracellular components such as DNA. In another pathway, the synergistic effect largely disturbed bacterial metabolism by regulating relative metabolic genes, followed by enhancing ROS generation to cause intracellular GSH depletion and DNA damage. More importantly, the synergistic effect significantly diminished the drug resistance of MRSA by downregulating the expression of the drug-resistant gene mecA and some relative multidrug efflux pumps (e.g., SepA and Tet38). An in vivo evaluation using a rat model with MRSA-infected wounds indicated that the synergistic photothermal and NO effect of GNS/HPDA-BNN6 can effectively eliminate MRSA from wounds, thereby alleviating inflammation and promoting wound healing. STATEMENT OF SIGNIFICANCE: Multidrug-resistant (MDR) bacteria have become a big threat to mankind, and therefore, the development of innovative antibacterial agents with high antibacterial efficiency is urgently required. Nanomaterial-mediated nitric oxide (NO) therapy is a promising strategy to effectively combat MDR bacteria through a synergistic antibacterial effect. Here, a gold nanostar/hollow polydopamine Janus nanostructure with precise near infrared (NIR) light-controlled NO release property (GNS/HPDA-BNN6) was developed. Both in vitro and in vivo evaluations demonstrated that GNS/HPDA-BNN6 could effectively eliminate methicillin-resistant Staphylococcus aureus (MRSA) from infected wounds and promote wound healing through a synergistic photothermal and NO therapeutic effect. Remarkably, the synergistic effect significantly diminished the drug resistance of MRSA by downregulating the expression of some drug-resistant genes and multidrug efflux pumps.